|Year : 2018 | Volume
| Issue : 19 | Page : 2338-2345
Common Injuries and Repair Mechanisms in the Endothelial Lining
Ling-Bing Meng1, Kun Chen2, Yuan-Meng Zhang3, Tao Gong1
1 Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
2 National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
3 Department of Internal Medicine, Jinzhou Medical University, Jinzhou, Liaoning 121001, China
|Date of Submission||23-Apr-2018|
|Date of Web Publication||21-Sep-2018|
Department of Neurology, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dong Dan, Beijing 100730
Source of Support: None, Conflict of Interest: None
Objective: Endothelial cells (ECs) are important metabolic and endocrinal organs which play a significant role in regulating vascular function. Vascular ECs, located between the blood and vascular tissues, can not only complete the metabolism of blood and interstitial fluid but also synthesize and secrete a variety of biologically active substances to maintain vascular tension and keep a normal flow of blood and long-term patency. Therefore, this article presents a systematic review of common injuries and healing mechanisms for the vascular endothelium.
Data Sources: An extensive search in the PubMed database was undertaken, focusing on research published after 2003 with keywords including endothelium, vascular, wounds and injuries, and wound healing.
Study Selection: Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize common injury and repair processes of the endothelial lining.
Results: Endothelial injury is closely related to the development of multiple cardiovascular and cerebrovascular diseases. However, the mechanism of vascular endothelial injury is not fully understood. Numerous studies have shown that the mechanisms of EC injury mainly involve inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, and molecular changes. Endothelial progenitor cells play an important role during the process of endothelial repair after such injuries. What's more, a variety of restorative cells, changes in cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training protect the endothelial lining by reducing the inducing factors, inhibiting inflammation and oxidative stress reactions, and delaying endothelial caducity.
Conclusions: ECs are always in the process of being damaged. Several therapeutic targets and drugs were seeked to protect the endothelium and promote repair.
Keywords: Endothelium; Vascular; Wound Healing; Wounds and Injuries
|How to cite this article:|
Meng LB, Chen K, Zhang YM, Gong T. Common Injuries and Repair Mechanisms in the Endothelial Lining. Chin Med J 2018;131:2338-45
| Introduction|| |
In recent years, cardiovascular disease has become the leading cause of disability and death among both urban and rural residents in China, driven largely by aging, diabetes, hypertension, hyperlipidemia, obesity, and smoking. However, vascular endothelial injury is also ubiquitous in atherosclerosis, hypertension, diabetic vascular complications, and several cardiovascular and cerebrovascular diseases. Endothelial cells (ECs) are important components of blood vessels, as they are arranged in a single vertical layer and are common targets in the development of cardiovascular disease. They not only form a barrier against allogenic material but also possess endocrine and immunological competence. Furthermore, they play an important role in vascular homeostasis, including by participating in vasoconstriction and vasodilation to control blood pressure, coagulation, atherosclerosis, and angiogenesis. Missing or dysfunctional ECs will expose damaged blood vessels to a variety of pathogenic factors so that the endogenous and extrinsic coagulation,,, pathway is activated, and local thrombosis produces vessel stenosis or occlusion. At the same time, various inflammatory dielectrics, cytokines, and chemokines are produced around the damaged vessels. Under the stimulation of these factors, smooth muscle cells proliferate, leading to endothelial hyperplasia and complications of hemadostenosis which can endanger the patient's life.
However, it is unclear which key factors or links among them trigger endothelial injury and repair. Therefore, several studies have explored the characteristics and mechanisms of endothelial injury, as well as investigating the roles of the harmful or beneficial substances secreted by a damaged endothelium. The current research on endothelial injury chiefly focuses on inflammatory reactions, physical stimulations, chemical poisons, concurrency of related diseases, and molecular changes. On the other hand, ECs also possess the ability to proliferate and repair themselves. A variety of restorative cells, changes to cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training can be beneficial to endothelial wound repair [Figure 1]. The research progress in both endothelial injury and repair is described below.
|Figure 1: The diagrammatic drawing in regard to the injury and repair in the common status of endothelial lining. →: Promote; (-): Inhibition. EC: Endothelial cells; EPCs: Endothelial progenitor cells; EMS: Electric muscle stimulation; HSCs: Hematopoietic stem cells; ECFCs: Endothelial colony forming cells; EOCs: Early outgrowth cells; NO: Nitric oxide; hAECs: Human amniotic epithelial cells; ADSCs: Adipose-derived stem cells; Tang: Angiogenic T cells; HBMP–2: Human bone morphogenic protein-2; MSCs: Mesenchymal stromal cells; eNOS: Endothelial nitric oxide synthase; apoA-I: Apolipoprotein A-I; HO-1: Heme oxygenase-1; ZFP580: Zinc finger transcription factor; H2O2: Hydrogen peroxide; IL-8: Interleukin-6; TNF: Tumor necrosis factor; sCD40L: Soluble CD40 ligand; MCP-1: Monocyte chemoattractant protein-1; IL-6: Interleukin-6; ZnO: Zinc oxide; VEGFR2: Vascular endothelial growth factor receptor 2; CXCR4: CXC chemokine receptor 4; s-ICAM1: Soluble intercellular adhesion molecule 1; ROS: Reactive oxygen species; NADPH: Nicotinamide adenine dinucleotide phosphate; MnSOD: Manganese superoxide dismutase.|
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| Protective Factors Related to Endothelial Repair|| |
Endothelial progenitor cells
Since the initial discovery of endothelial progenitor cells (EPCs), researchers have made meaningful progress toward a strict functional description and a better interpretation of EPCs, which have been successfully used to stimulate vascular repair and angiogenesis in some experimental settings.,,,, Moreover, EPC-containing products (such as bone marrow or mobilized peripheral blood), which are a kind of human autologous cell therapies, have proven to be viable and valid options in the treatment of atherosclerotic disease. Furthermore, significantly higher levels of circulating CD34+ KDR+ cells are consistent with the number of EPCs improving endothelial repair. Thus, CD34+ KDR+ cells may become the key to successful therapies that require targeting several parallel mechanisms for a long time. They are also integral to novel molecular strategies and translational developments of cerebrovascular treatments in patients with type 2 diabetes mellitus. Since circulating CD34+ cells have been reported to be beneficial to endothelial repair (and thus to vascular repair and the development of atherosclerosis), this factor could be a biomarker for the activity of the vicious between endothelial damage and hypertension common in elderly men.
What's more, external electric muscle stimulation (EMS) reduced symptoms of vascular lesions induced by diabetic neuropathy and decreased diastolic blood pressure. A single EMS remedy fortified the function of certain molecules which can mediate differentiation and attachment on the surface of hematopoietic stem cells (HSCs) during blood circulation. A new assumption is that the EMS-induced increase in surface attachment molecules on HSCs allows the HSCs to leave blood circulation and that the EMS remedy boosts the effect of EPCs and HSCs. However, the downregulation of Notch1 also enhanced the proliferation, differentiation, migration, and adhesion of EPCs, along with the capacity to form human vein ECs. In spite of a number of studies revealing correlations between circulating EPC phenotypes and patient traits and prognosis, the pathophysiological effect of circulating EPC concentrations is still unclear.
Other correlative cells
Endothelial repair can be considered from the cell's perspective as a result of the lesions originating from ECs. Recent evidence illuminates the presence of two EPC subtypes: endothelial colony-forming cells (ECFCs) and early outgrowth cells (EOCs). Their different morphological and phenotypic characteristics, and more importantly, the release of the antiaggregating agents prostacyclin 2 and nitric oxide (NO) in each EPC subtype, are implicated in their respective roles in endothelial function and thus may be linked to the better efficiency of ECFCs in inhibiting endothelial injury during endothelial regeneration., First, in vascular regenerative medicine, human amniotic epithelial cells (hAECs) are a promising means for endothelial repair. Vácz et al. concluded that, without immunosuppression, hAECs were capable of intruding into the vascular wall but were incapable of enhancing vascular condition. She emphasized that this process can achieve the aim of morphological implantation and cannot gain the functional benefits, highlighting the necessity to research other theories of endothelial repair. In addition, Hasdemir et al. proposed that, after a radiation injury, adipose-derived stem cells have an underlying capacity for strengthening hemokinesis, which might be accompanied with endothelial repair and needs further study. More recently, angiogenic T cells (Tang) have been recently discovered to cooperate with EPCs in endothelial repair. The main aim of Rodríguez-Carrio et al.'s research was to analyze the Tang and EPC numbers in relation to traditional cerebrovascular risk factors. The increase of Tang has a protective effect on the endothelium. At present, cell replacement therapy is an idealized and novel strategy for endothelial injury, but there are also numerous obstacles and difficulties such as immunological rejection, ethical issues involving embryos, and a limited number of cells.
Cytokines or molecules
From a microscopic perspective, molecular expression plays an important role in endothelial repair. In the case of irradiation in rats, severe endothelial injury was produced, but treatment with human bone morphogenic protein-2 (HBMP-2) combined with mesenchymal stromal cells (MSCs) accelerated repair. By regulating hypoxia-inducible factor-1 α expression (which influences endothelial formation and recovery), and by upregulating the expression of the endothelial NO synthase (eNOS) pathway, HBMP-2 exerts its effect. These findings suggest that novel methods for adding molecules or cytokines to MSCs should be evaluated for remedying chronic radiation-induced damage to the endothelium.
Apolipoprotein A-I (apoA-I) mimetic peptide has many antiatherogenic features which improve the impaired endothelial proliferation and migration resulting from oxidized low-density lipoprotein, by reducing EC apoptosis and upregulating the expression of heme oxygenase-1 (HO-1) and eNOS. Moreover, the antioxidation, proproliferation, and promigration abilities of apoA-I were cut down by the inhibitors of both eNOS and HO-1. Next, increasing high-density lipoprotein (HDL) concentrations by inhibiting the cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelia in damaged aortas in a scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner. In summary, the results suggest that apoA-I and cholesteryl ester transfer protein inhibition might be commendable candidates for the protection of ECs and the prevention of atherosclerotic disease.
Along similar lines, novel zinc finger transcription factor (ZFP580) facilitates not only the differentiation of EPCs into ECs by upregulating the availability of NO and the expression of eNOS but also endothelial formation. This may demonstrate a new theory of ZFP580 in EPC evolution and its meaningful value in the remedy of vascular damage. Adepu et al.'s research shows that early injury in transplanted kidneys causes repair stimulations, specifically tubular syndecan-1 expression for endothelial neogenesis. Syndecan-1 is a transmembrane heparan sulfate proteoglycan involved in regenerative growth and cellular adhesion. Increased serum syndecan-1 concentrations might be a repair factor relevant to endothelial function. Moreover, bone marrow-derived cellular therapies are a new and developing strategy to improve therapeutic endothelial neogenesis in atherosclerotic disease. Specifically, ixmyelocel-T is manufactured from a small sample of bone marrow aspirate, forming an expanded autologous multicellular therapy. Ledford et al. reported that ixmyelocel-T cooperates with ECs in a paracrine manner, leading to endothelial protection and angiogenesis. This result shows that ixmyelocel-T could be beneficial for improving endothelial repair in ischemic cardiovascular and cerebrovascular diseases. In a word, ixmyelocel-T treatment may offer a novel insight into remedial vasculogenesis in patient populations requiring an increased number of reborn cells.
Endothelial-protective chemical drugs, including lipid-lowering medicines, anti-human immunodeficiency virus (HIV) drugs, hypoglycemic drugs, hypotensor, and Vitamin D, play a role in endothelial repair mainly by treating concomitant diseases, which can achieve better results. First, in terms of lipid-lowering medicines, present clinical worries center on restraining the proliferation of smooth muscle cells by utilizing drug-eluting stents. It is unfortunate that this approach can also suppress endothelial proliferation and prevent EC repair. However, Hussner's data offered enough proof and a theoretical basis for using atorvastatin in stents to avoid this dilemma. Furthermore, Li et al. researched the capacity of atorvastatin to guard ECFCs, a subtype of EPCs, and to demonstrate a potential protective effect from hydrogen peroxide (H2O2)-induced oxidative injury. Furthermore, Rosuvastatin improved re-endothelialization by regulation of EPCs, proposing that facilitating endothelial recovery offers a fresh therapeutic strategy for vascular repair.
Second, one study demonstrates that anti-HIV drugs can promote the repair of impaired endothelia. Recovery of the serum concentration of EPCs was higher in darunavir-remedied individuals than in those remedied with rilpivirine, suggesting promising endothelial repair methods. Third, hypoglycemic medicine can effectively reduce blood glucose concentrations, weaken the damage of high sugar on ECs, and form an endothelial protection mechanism. Metformin has an underlying endothelium-protective function through promoting the level of EPCs and EC and markedly affecting hypoglycemic function. Similarly, irisin was proven to promote endothelial regeneration in diabetic mice that received EPC transplants after vascular damage. Fourth, store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays a part in all kinds of cell activities. SOCE inhibition can have a favorable influence on EPCs after exposure to oxidative stress caused by oxidizing agents and may provide an underlying method to compete with endothelial damage. Fifth, in Reynolds et al.'s experimental research, calcitriol promoted endothelial repair in individuals with systemic lupus erythematosus (SLE). The results demonstrate that Vitamin D could be a new treatment to decrease atherosclerotic disease and protect the ECs from damage., Recently, there have been some new reports that the prostacyclin has a certain role in the repair of endothelial injury, but it is not very clear and needs further study.
Other approaches to endothelial repair
The repair of the endothelium involves a variety of aspects including certain RNAs, regulation of blood pressure, physical fitness training, number of blood platelets, and physical stimulation. Although the whole network of microRNAs (miRNAs) involved in the process is still largely unknown, present evidence shows that therapeutic replacement of 23 miRNAs, miR-126-5p, miR-155, and other miRNAs, which help maintain the vascular homeostasis of EPCs, may restore endothelial health and reduce atherosclerosis.,, Furthermore, hypertension might indicate an insufficient ability for adequate vascular maintenance, so lowering blood pressure is a protective strategy and a therapeutic prospect for repairing damaged vascular ECs.,,, Next, the number and activity of ECs in men and increased CD34+ cells in women are enhanced through exercise.,,, Finally, as to physical stimulation, external EMS, shear stress, and hypoxia are vital nonpharmacologic methods to improve the activity of EPCs. These findings provide novel nonpharmacologic therapeutic methods for hypertension-interrelated endothelial neogenesis.
| Risk Factors Related with Endothelial Injury|| |
Numerous studies have demonstrated that the pathophysiological processes of various cardiovascular and cerebrovascular diseases, such as atherosclerosis, involve inflammatory responses., Mitsides et al. proved that inflammation reactions were mediated through the interleukin-8 (IL-8) pathway forecasted microvascular endothelial injury, but fms-like tyrosine kinase-1 (Flt-1), which is a potential marker of angiogenesis and endothelial repair, might have a remarkable protective function. Further cognition of IL-8 and Flt-1 will be inevitable to improve the stationary state of vessels. Except for IL-8, which can exert a harmful effect on ECs, there are some aspects relevant to the relationship between inflammation and endothelial injury. To start with, as a characteristic of rheumatoid arthritis, inflammation results in the activation of ECs, which can cause atherosclerosis by means of prompting leukocyte adhesion molecules to overexpress. Endothelial dysfunction, induced by inflammation, interferes with endothelial repair courses. Accardi et al. argued that inflamm-ageing, the chronic low-grade inflammation that is common in elderly populations, complicates general vascular condition and gives rise to atherosclerosis, the main predictor of cardiovascular and cerebrovascular diseases. As a matter of course, oxidative stress and inflammation play an essential part in the pathogenic mechanism of endothelial injury, generally due to the reduced availability of NO.
Finally, it is worth mentioning that the underlying influences of Tan II A on tumor necrosis factor (TNF)-α-motivated EPC proliferation, formation ability, and paracrine activity in vitro tubes, as demonstrated by Wang et al. The results predicted that TNF-α damaged EPC proliferation competence and neovascularization capacity in vitro and boosted the EPC excretion of inflammation factors such as soluble CD40 ligand, monocyte chemoattractant protein-1, and IL-6. Nevertheless, these effects were able to be reversed by Tan II A. In other words, these results proved that Tan II A may possess the ability to defend EPCs from lesions triggered by TNF-α. Consequently, these findings may offer proof for the theoretical foundation of Tan II A and its underlying value to prevent and remedy early atherosclerotic disease related to EPC and endothelial injury. In brief, the infiltration and activity of inflammatory cells have been key factors in endothelial injury.
Physical stimulation refers to external changes in the body or the natural environment, including knocking, pressure, pulling, fire, ice, radiation, metal ions, and body type changes. However, damage to ECs mainly includes the following aspects. Pradhan et al. found that radiation during childhood cancer treatment boosts the risk for cardiovascular and cerebrovascular diseases among adult survivors, which is considered to be mediated by the injury to the ECs. ECFCs, a population of EPCs, exhibited some changes after exposure to radiation. ECFCs and EPCs in the individuals receiving radiation therapy were significantly lower (P < 0.05) than those without radiotherapy. The elementary results of this research provide proof that ECFCs function as biological targets for endothelial damage. In addition, interventional therapy, mainly device implants, markedly decreases the incidence of restenosis and the necessity for vascular remodeling but is related with impaired ECs. Namely, the constant presence of a metal stent or spring coil may injure the proliferation of ECs. The hysteresis effect of intervention operation on endothelial damage was discussed by Tesfamariam. Furthermore, another finding implied that zinc oxide nanoparticles restrain angiogenesis from ECFCs by downregulating the expression of receptors associated with angiogenesis including the vascular endothelial growth factor receptor (VEGFR), the VEGFR2, and the CXC chemokine receptor 4. The influences are on the condition of levels of secreted Zn(II). Finally, it was surprising that obese patients presented with high concentrations of adipokines, plenty of endothelial microparticles, and a low number of EPCs, with more augmentation in adipokines after surgical stimulation, indicating an inflammatory situation that deteriorates after surgical stimulation and may influence endothelial repair. Physical stimulation, an important factor in endothelium damage, should be avoided as much as possible.
The role of chemical toxicants in endothelial injury is also significant, including indoxyl sulfate, nicotine, reactive oxygen, H2O2, and oxidative stress. Carmona et al.'s findings confirmed that indoxyl sulfate is associated with the poor prognosis of chronic kidney disease and cardiovascular disease owing to the injury of endotheliocytes, and that it is able to promote the formation of endothelial vesicles with varying molecules that maintain the homeostasis of EPCs. These particular traits of endothelial vesicles could be regarded as original biological targets for a diagnosis of atherosclerotic disease. In addition, as we all know, smoking is harmful to our health. Specifically, nicotine concentrations in hair were dramatically negatively interrelated with total antioxidant capacity levels of HDL and EPCs, after controlling for body mass index, age, sex, education, and consumption patterns. Moreover, nicotine exposure during adolescence is disadvantageous to the vascular endothelium simply because intercellular adhesion molecule 1 is a biomarker for endothelial excitation and stress after damage to the endothelium.
Oxidative stress also plays a primary part in the pathogenic mechanism of endothelial damage, generally owing to the attenuated availability of NO. Furthermore, H2O2 can induce oxidative stress to weaken the protective condition of EPCs. Amassing reactive oxygen species (ROS) can do some harm in the repair of impaired endotheliocytes, but the potential theory is undiscovered. EOCs play an important role in endothelial repair. Research findings show that p66Shc overexpression induced by ROS, through the nicotinamide adenine dinucleotide phosphate/manganese superoxide dismutase (MnSOD) axis, impairs the paracrine angiogenic potential of aged EOCs to aggravate endothelial injury. In short, the damage from chemical poisons is widespread, causing ECs to be stripped, losing their invisible protective barrier, and forming atherosclerosis. These findings form the basis for novel therapeutic strategies to improve vascular repair after injury and combat atherosclerotic disease in the early stages.
Other relevant factors in endothelial injury
There are many connections between the upregulation of SM22alpha promoter, sympathoadrenal activation, Red Cell Distribution, aging, Vitamin D deficiency, and SOCE. Whether these factors or their interactions will produce injury to the endothelium needs to be studied further in the future [Table 1].,,,,,
| Concurrency of Related Diseases on Endothelial Injury|| |
Diseases of some other systems can be accompanied by endothelial injury, such as chronic obstructive pulmonary disease,, sepsis, SLE, obstructive sleep apnea, end-stage renal disease, left ventricular hypertrophy, Blackfoot disease,, and type 2 diabetes, [Table 1]. It may be that many diseases are connected to endothelial injuries to varying degrees, but uncovering those connections will require tireless scientific efforts.
| Conclusion|| |
Endothelial injury is an important pathophysiological step toward atherosclerotic stenosis, an overhealing reaction of the blood vessels to the injury., Studies have shown that various factors can lead to damage of the endothelium, including inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, aging, and a deficiency of Vitamin D.,,,, However, the exact mechanism of endothelial injury is not yet fully understood.
Repairing endothelial injury and recovering endothelial function are considered to be the keys to the prevention and treatment of atherosclerotic stenosis., Numerous studies have confirmed that several different sources of EPCs are transplanted to the damaged blood vessel; these EPCs can locate the vascular lesions, mediate vessels to be endothelial, and inhibit neointimal hyperplasia., Through the deepening of endothelial injury and repair research, especially in terms of changes in cytokines and molecules, chemical drugs, certain lipid pathways, certain RNAs, regulation of blood pressure, and physical fitness training, new targets for the protection of the vascular endothelium will be found to produce new drugs for the protection of damaged endothelia.
We are grateful to Peng Guo, from the Fourth Hospital of Hebei Medical University, for technical help about the use of software. And the general support by the chairman of Neurology Department of Beijing Hospital is thanked.
Financial support and sponsorship
This work was supported by a grant from the National Natural Science Foundation of China (No. 31271097).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al.
2016 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. The sixth joint task force of the European Society of Cardiology and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts. Developed with the special contribution of the European Association for Cardiovascular Prevention and Rehabilitation. G Ital Cardiol (Rome) 2017;18:547-612. doi: 10.1714/2729.27821.
Lebaschi A, Nakagawa Y, Wada S, Cong GT, Rodeo SA. Tissue-specific endothelial cells: A promising approach for augmentation of soft tissue repair in orthopedics. Ann N
Y Acad Sci 2017;1410:44-56. doi: 10.1111/nyas.13575.
Bach LA. Endothelial cells and the IGF system. J Mol Endocrinol 2015;54:R1-13. doi: 10.1530/jme-14-0215.
Blasi A, Reverter JC. Time to change the classical vision of coagulation in liver disease: From the balance disequilibrium to systems biology network modeling. Minerva Anestesiol 2018;84:848-57. doi: 10.23736/s0375-9393.17.12313-8.
Doğan HO, Büyüktuna SA, Kapancik S, Bakir S. Evaluation of the associations between endothelial dysfunction, inflammation and coagulation in crimean-congo hemorrhagic fever patients. Arch Virol 2018;163:609-16. doi: 10.1007/s00705-017-3653-1.
Chen DC. Sepsis and intestinal microvascular endothelial dysfunction. Chin Med J 2017;130:1137-8. doi: 10.4103/0366-6999.205865.
] [Full text]
Ikeda M, Matsumoto H, Ogura H, Hirose T, Shimizu K, Yamamoto K, et al.
Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis. J Crit Care 2018;43:48-53. doi: 10.1016/j.jcrc.2017.07.049.
Trommer S, Leimert A, Bucher M, Schumann J. Impact of unsaturated fatty acids on cytokine-driven endothelial cell dysfunction. Int J Mol Sci 2017;18. pii: E2739. doi: 10.3390/ijms18122739.
Takizawa S, Nagata E, Nakayama T, Masuda H, Asahara T. Recent progress in endothelial progenitor cell culture systems: Potential for stroke therapy. Neurol Med Chir (Tokyo) 2016;56:302-9. doi: 10.2176/nmc.ra.2016-0027.
Hu CH, Ke X, Chen K, Yang DY, Du ZM, Wu GF, et al.
Transplantation of human umbilical cord-derived endothelial progenitor cells promotes re-endothelialization of the injured carotid artery after balloon injury in New Zealand white rabbits. Chin Med J 2013;126:1480-5. doi: 10.3760/cma.j.issn.0366-6999.20122355.
Valencia-Nuñez DM, Kreutler W, Moya-Gonzalez J, Alados-Arboledas P, Muñoz-Carvajal I, Carmona A, et al.
Endothelial vascular markers in coronary surgery. Heart Vessels 2017;32:1390-9. doi: 10.1007/s00380-017-1006-3.
Nielsen N, Laustsen C, Bertelsen LB. 13C dynamic nuclear polarization for measuring metabolic flux in endothelial progenitor cells. Exp Cell Res 2016;349:95-100. doi: 10.1016/j.yexcr.2016.10.002.
Zhu J, Duan G, Lang L, Liu Y, Zhu J, Wang H, et al.
The bacterial component flagellin induces anti-sepsis protection through TLR-5, IL-1RN and VCAN during polymicrobial sepsis in mice. Cell Physiol Biochem 2015;36:446-56. doi: 10.1159/000430111.
Kuschnerus K, Landmesser U, Kränkel N. Vascular repair strategies in type 2 diabetes: Novel insights. Cardiovasc Diagn Ther 2015;5:374-86. doi: 10.3978/j.issn.2223-3652.2015.05.11.
Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, et al.
Platelets and circulating CD34-positive cells as an indicator of the activity of the vicious cycle between hypertension and endothelial dysfunction in elderly Japanese men. Atherosclerosis 2017;259:26-31. doi: 10.1016/j.atherosclerosis.2017.02.016.
Hidmark A, Spanidis I, Fleming TH, Volk N, Eckstein V, Groener JB, et al.
Electrical muscle stimulation induces an increase of VEGFR2 on circulating hematopoietic stem cells in patients with diabetes. Clin Ther 2017;39:1132-4400. doi: 10.1016/j.clinthera.2017.05.340.
Liu X, Luo Q, Zheng Y, Liu X, Hu Y, Liu W, et al.
Notch1 impairs endothelial progenitor cell bioactivity in preeclampsia. Reprod Sci 2016. pii: 1933719116648411. doi: 10.1177/1933719116648411.
Bou Khzam L, Bouchereau O, Boulahya R, Hachem A, Zaid Y, Abou-Saleh H, et al.
Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation. J Transl Med 2015;13:353. doi: 10.1186/s12967-015-0723-6.
Sradnick J, Rong S, Luedemann A, Parmentier SP, Bartaun C, Todorov VT, et al.
Extrarenal progenitor cells do not contribute to renal endothelial repair. J Am Soc Nephrol 2016;27:1714-26. doi: 10.1681/asn.2015030321.
Vácz G, Cselenyák A, Cserép Z, Benkő R, Kovács E, Pankotai E, et al.
Effects of amniotic epithelial cell transplantation in endothelial injury. Interv Med Appl Sci 2016;8:164-71. doi: 10.1556/1646.8.2016.4.6.
Hasdemir M, Agir H, Eren GG, Aksu MG, Alagoz MS, Duruksu G, et al.
Adipose-derived stem cells improve survival of random pattern cutaneous flaps in radiation damaged skin. J Craniofac Surg 2015;26:1450-5. doi: 10.1097/scs.0000000000001852.
Rodríguez-Carrio J, Alperi-López M, López P, Alonso-Castro S, Ballina-García FJ, Suárez A, et al.
Angiogenic T cells are decreased in rheumatoid arthritis patients. Ann Rheum Dis 2015;74:921-7. doi: 10.1136/annrheumdis-2013-204250.
François S, Eder V, Belmokhtar K, Machet MC, Douay L, Gorin NC, et al.
Synergistic effect of human bone morphogenic protein-2 and mesenchymal stromal cells on chronic wounds through hypoxia-inducible factor-1 α induction. Sci Rep 2017;7:4272. doi: 10.1038/s41598-017-04496-w.
Yin X, Liang Z, Yun Y, Pei L. Intravenous transplantation of BMP2-transduced endothelial progenitor cells attenuates lipopolysaccharide-induced acute lung injury in rats. Cell Physiol Biochem 2015;35:2149-58. doi: 10.1159/000374020.
Liu D, Ding Z, Wu M, Xu W, Qian M, Du Q, et al.
The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway. J Mol Cell Cardiol 2017;105:77-88. doi: 10.1016/j.yjmcc.2017.01.017.
Wu BJ, Shrestha S, Ong KL, Johns D, Hou L, Barter PJ, et al.
Cholesteryl ester transfer protein inhibition enhances endothelial repair and improves endothelial function in the rabbit. Arterioscler Thromb Vasc Biol 2015;35:628-36. doi: 10.1161/atvbaha.114.304747.
Wei S, Huang J, Li Y, Zhao J, Luo Y, Meng X, et al.
Novel zinc finger transcription factor ZFP580 promotes differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells via eNOS/NO pathway. J Mol Cell Cardiol 2015;87:17-26. doi: 10.1016/j.yjmcc.2015.08.004.
Adepu S, Rosman CW, Dam W, van Dijk MC, Navis G, van Goor H, et al.
Incipient renal transplant dysfunction associates with tubular syndecan-1 expression and shedding. Am J Physiol Renal Physiol 2015;309:F137-45. doi: 10.1152/ajprenal.00127.2015.
Ledford KJ, Murphy N, Zeigler F, Bartel RL, Tubo R. Therapeutic potential of ixmyelocel-T, an expanded autologous multicellular therapy for treatment of ischemic cardiovascular diseases. Stem Cell Res Ther 2015;6:25. doi: 10.1186/s13287-015-0007-3.
McDonald AI, Iruela-Arispe ML. Healing arterial ulcers: Endothelial lining regeneration upon vascular denudation injury. Vascul Pharmacol 2015;72:9-15. doi: 10.1016/j.vph.2015.06.007.
Li DW, Li JH, Wang YD, Li GR. Atorvastatin protects endothelial colony-forming cells against H2O2-induced oxidative damage by regulating the expression of annexin A2. Mol Med Rep 2015;12:7941-8. doi: 10.3892/mmr.2015.4440.
Liu P, An Q, Chen X, Huang J, Yang GY, Zhu W, et al.
Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: Promotion of endothelial progenitor cells in a rodent model. J Neurosurg 2016;124:1265-74. doi: 10.3171/2015.3.jns142841.
Echeverría P, Gómez-Mora E, Roura S, Bonjoch A, Puig J, Pérez-Alvarez N, et al.
Variable endothelial cell function restoration after initiation of two antiretroviral regimens in HIV-infected individuals. J Antimicrob Chemother 2017;72:2049-54. doi: 10.1093/jac/dkx074.
Ahmed FW, Rider R, Glanville M, Narayanan K, Razvi S, Weaver JU, et al.
Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study. Cardiovasc Diabetol 2016;15:116. doi: 10.1186/s12933-016-0413-6.
Zhu G, Wang J, Song M, Zhou F, Fu D, Ruan G, et al.
Irisin increased the number and improved the function of endothelial progenitor cells in diabetes mellitus mice. J Cardiovasc Pharmacol 2016;68:67-73. doi: 10.1097/fjc.0000000000000386.
Wang YW, Zhang JH, Yu Y, Yu J, Huang L. Inhibition of store-operated calcium entry protects endothelial progenitor cells from H2O2-induced apoptosis. Biomol Ther (Seoul) 2016;24:371-9. doi: 10.4062/biomolther.2015.130.
Reynolds J, Ray D, Alexander MY, Bruce I. Role of Vitamin D in endothelial function and endothelial repair in clinically stable systemic lupus erythematosus. Lancet 2015;385 Suppl 1:S83. doi: 10.1016/s0140-6736(15)60398-1.
Reynolds JA, Haque S, Williamson K, Ray DW, Alexander MY, Bruce IN, et al.
Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus. Sci Rep 2016;6:22341. doi: 10.1038/srep22341.
Gybel-Brask M, Rasmussen R, Stensballe J, Johansson PI, Ostrowski SR. Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage. Acta Neurochir (Wien) 2017;159:1073-8. doi: 10.1007/s00701-017-3168-2.
Natarelli L, Schober A. MicroRNAs and the response to injury in atherosclerosis. Hamostaseologie 2015;35:142-50. doi: 10.5482/hamo-14-10-0051.
Carmona A, Guerrero F, Buendia P, Obrero T, Aljama P, Carracedo J, et al.
Microvesicles derived from indoxyl sulfate treated endothelial cells induce endothelial progenitor cells dysfunction. Front Physiol 2017;8:666. doi: 10.3389/fphys.2017.00666.
Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, et al.
Height is an indicator of vascular maintenance capacity in older men. Geriatr Gerontol Int 2017;17:1729-36. doi: 10.1111/ggi.12876.
Bai YP, Xiao S, Tang YB, Tan Z, Tang H, Ren Z, et al.
Shear stress-mediated upregulation of GTP cyclohydrolase/tetrahydrobiopterin pathway ameliorates hypertension-related decline in reendothelialization capacity of endothelial progenitor cells. J Hypertens 2017;35:784-97. doi: 10.1097/hjh.0000000000001216.
Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, et al.
Possible mechanism underlying the association between higher hemoglobin level and hypertension in older Japanese men. Geriatr Gerontol Int 2017;17:2586-92. doi: 10.1111/ggi.13068.
Shimizu Y, Sato S, Noguchi Y, Koyamatsu J, Yamanashi H, Nagayoshi M, et al.
Triglycerides and blood pressure in relation to circulating CD34-positive cell levels among community-dwelling elderly Japanese men: A cross-sectional study. Environ Health Prev Med 2017;22:77. doi: 10.1186/s12199-017-0684-x.
Lansford KA, Shill DD, Dicks AB, Marshburn MP, Southern WM, Jenkins NT, et al.
Effect of acute exercise on circulating angiogenic cell and microparticle populations. Exp Physiol 2016;101:155-67. doi: 10.1113/ep085505.
Recchioni R, Marcheselli F, Antonicelli R, Lazzarini R, Mensà E, Testa R, et al.
Physical activity and progenitor cell-mediated endothelial repair in chronic heart failure: Is there a role for epigenetics? Mech Ageing Dev 2016;159:71-80. doi: 10.1016/j.mad.2016.03.008.
Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, et al.
Handgrip strength and subclinical carotid atherosclerosis in relation to platelet levels among hypertensive elderly Japanese. Oncotarget 2017;8:69362-9. doi: 10.18632/oncotarget.20618.
Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, et al.
Platelets as an indicator of vascular repair in elderly Japanese men. Oncotarget 2016;7:44919-26. doi: 10.18632/oncotarget.10229.
Nishimura R, Nishiwaki T, Kawasaki T, Sekine A, Suda R, Urushibara T, et al.
Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung. Am J Physiol Lung Cell Mol Physiol 2015;308:L746-58. doi: 10.1152/ajplung.00243.2014.
Lai CL, Xing JP, Liu XH, Qi J, Zhao JQ, Ji YR, et al.
Relationships of inflammatory factors and risk factors with different target organ damage in essential hypertension patients. Chin Med J 2017;130:1296-302. doi: 10.4103/0366-6999.206343.
] [Full text]
Xiong XD, Xiong WD, Xiong SS, Chen GH. Research progress on the risk factors and outcomes of human carotid atherosclerotic plaques. Chin Med J 2017;130:722-9. doi: 10.4103/0366-6999.201598.
] [Full text]
Mitsides N, Cornelis T, Broers NJH, Diederen NMP, Brenchley P, Heitink-Ter Braak N, et al.
Inflammatory and angiogenic factors linked to longitudinal microvascular changes in hemodialysis patients irrespective of treatment dose intensity. Kidney Blood Press Res 2017;42:905-18. doi: 10.1159/000485048.
Yang X, Chang Y, Wei W. Endothelial dysfunction and inflammation: Immunity in rheumatoid arthritis. Mediators Inflamm 2016;2016:6813016. doi: 10.1155/2016/6813016.
Accardi G, Aiello A, Gambino CM, Virruso C, Caruso C, Candore G, et al.
Mediterranean nutraceutical foods: Strategy to improve vascular ageing. Mech Ageing Dev 2016;159:63-70. doi: 10.1016/j.mad.2016.02.007.
Wang XX, Yang JX, Pan YY, Zhang YF. Protective effects of tanshinone II A on endothelial progenitor cells injured by tumor necrosis factor-α. Mol Med Rep 2015;12:4055-62. doi: 10.3892/mmr.2015.3969.
Pradhan K, Mund J, Case J, Gupta S, Liu Z, Gathirua-Mwangi W, et al.
Differences in circulating endothelial progenitor cells among childhood cancer survivors treated with and without radiation. J Hematol Thromb 2015;1. pii: 4. doi: 10.13188/2380-6842.1000005.
Zhang H, Tao Y, Ren S, Liu H, Zhou H, Hu J, et al.
Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells. Exp Ther Med 2017;14:4160-6. doi: 10.3892/etm.2017.5035.
Tesfamariam B. Endothelial repair and regeneration following intimal injury. J Cardiovasc Transl Res 2016;9:91-101. doi: 10.1007/s12265-016-9677-1.
Tada-Oikawa S, Ichihara G, Suzuki Y, Izuoka K, Wu W, Yamada Y, et al.
Zn (II) released from zinc oxide nano/micro particles suppresses vasculogenesis in human endothelial colony-forming cells. Toxicol Rep 2015;2:692-701. doi: 10.1016/j.toxrep.2015.04.003.
Noci MV, Ramírez R, Lluch M, Rodríguez M, Carracedo J. Changes in endothelial microparticles and endothelial progenitor cells in obese patients in response to surgical stress. J Bone Joint Surg Am 2015;97:353-8. doi: 10.2106/JBJS.N.00570.
Groner JA, Huang H, Joshi MS, Eastman N, Nicholson L, Bauer JA, et al.
Secondhand smoke exposure and preclinical markers of cardiovascular risk in toddlers. J Pediatr 2017;189:155-61. doi: 10.1016/j.jpeds.2017.06.032.
Groner JA, Huang H, Nagaraja H, Kuck J, Bauer JA. Secondhand smoke exposure and endothelial stress in children and adolescents. Acad Pediatr 2015;15:54-60. doi: 10.1016/j.acap.2014.09.003.
Paneni F, Costantino S, Kränkel N, Cosentino F, Lüscher TF. Reprogramming ageing and longevity genes restores paracrine angiogenic properties of early outgrowth cells. Eur Heart J 2016;37:1733-7. doi: 10.1093/eurheartj/ehw073.
Jing L, Wang W, Zhang S, Xie M, Tian D, Luo X, et al.
Targeted inhibitory effect of lenti-SM22alpha-p27-EGFP recombinant lentiviral vectors on proliferation of vascular smooth muscle cells without compromising re-endothelialization in a rat carotid artery balloon injury model. PLoS One 2015;10:e0118826. doi: 10.1371/journal.pone.0118826.
Wang LY, Zhang JH, Yu J, Yang J, Deng MY, Kang HL, et al.
Reduction of store-operated ca(2+) entry correlates with endothelial progenitor cell dysfunction in atherosclerotic mice. Stem Cells Dev 2015;24:1582-90. doi: 10.1089/scd.2014.0538.
Ostrowski SR, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al.
Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients. J Trauma Acute Care Surg 2017;82:293-301. doi: 10.1097/ta.0000000000001304.
Rodríguez-Carrio J, Alperi-López M, López P, Alonso-Castro S, Carro-Esteban SR, Ballina-García FJ, et al.
Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis. Atherosclerosis 2015;240:131-6. doi: 10.1016/j.atherosclerosis.2015.03.009.
Bochenek ML, Schütz E, Schäfer K. Endothelial cell senescence and thrombosis: Ageing clots. Thromb Res 2016;147:36-45. doi: 10.1016/j.thromres.2016.09.019.
Reynolds JA, Rosenberg AZ, Smith CK, Sergeant JC, Rice GI, Briggs TA, et al.
Brief report: Vitamin D deficiency is associated with endothelial dysfunction and increases type I interferon gene expression in a murine model of systemic lupus erythematosus. Arthritis Rheumatol 2016;68:2929-35. doi: 10.1002/art.39803.
Doyle MF, Tracy RP, Parikh MA, Hoffman EA, Shimbo D, Austin JH, et al.
Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema. PLoS One 2017;12:e0173446. doi: 10.1371/journal.pone.0173446.
Ng-Blichfeldt JP, Alçada J, Montero MA, Dean CH, Griesenbach U, Griffiths MJ, et al.
Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema. Thorax 2017;72:510-21. doi: 10.1136/thoraxjnl-2016-208846.
Yang Y, Haeger SM, Suflita MA, Zhang F, Dailey KL, Colbert JF, et al.
Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. Am J Respir Cell Mol Biol 2017;56:727-37 doi: 10.1165/rcmb.2016-0338OC.
Liu JJ, Dahlin BC, Waldau B. Contrast encephalopathy after coiling in the setting of obstructive sleep apnoea. BMJ Case Rep 2015;2015. pii: bcr2014207503. doi: 10.1136/bcr-2014-207503.
Lineen JR, Kuliszewski M, Dacouris N, Liao C, Rudenko D, Deva DP, et al.
Early outgrowth pro-angiogenic cell number and function do not correlate with left ventricular structure and function in conventional hemodialysis patients: A cross-sectional study. Can J Kidney Health Dis 2015;2:25. doi: 10.1186/s40697-015-0060-y.
Hu QS, Chen YX, Huang QS, Deng BQ, Xie SL, Wang JF, et al.
Carbon monoxide releasing molecule accelerates reendothelialization after carotid artery balloon injury in rat. Biomed Environ Sci 2015;28:253-62. doi: 10.3967/bes2015.036.
Nelson J, Wu Y, Jiang X, Berretta R, Houser S, Choi E, et al.
Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of β1-integrin in progenitor cell migration and adhesion. FASEB J 2015;29:3085-99. doi: 10.1096/fj.14-267989.
De Pascale MR, Bruzzese G, Crimi E, Grimaldi V, Liguori A, Brongo S, et al.
Severe type 2 diabetes induces reversible modifications of endothelial progenitor cells which are ameliorate by glycemic control. Int J Stem Cells 2016;9:137-44. doi: 10.15283/ijsc.2016.9.1.137.
He HL, Liu L, Chen QH, Cai SX, Han JB, Hu SL, et al.
MSCs modified with ACE2 restore endothelial function following LPS challenge by inhibiting the activation of RAS. J Cell Physiol 2015;230:691-701. doi: 10.1002/jcp. 24794.
Werner N, Junk S, Laufs U, Link A, Walenta K, Bohm M, et al.
Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res 2003;93:e17-24. doi: 10.1161/01.res.0000083812.30141.74.
Serruys PW, Strauss BH, Beatt KJ, Bertrand ME, Puel J, Rickards AF, et al.
Angiographic follow-up after placement of a self-expanding coronary-artery stent. N Engl J Med 1991;324:13-7. doi: 10.1056/nejm199101033240103.
Iqbal J, Gunn J, Serruys PW. Coronary stents: Historical development, current status and future directions. Br Med Bull 2013;106:193-211. doi: 10.1093/bmb/ldt009.
Pinto MT, Covas DT, Kashima S, Rodrigues CO. Endothelial mesenchymal transition: Comparative analysis of different induction methods. Biol Proced Online 2016;18:10. doi: 10.1186/s12575-016-0040-3.
Xu K, Xu C, Zhang Y, Qi F, Yu B, Li P, et al.
Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection. Theranostics 2018;8:437-49. doi: 10.7150/thno.22467.
Tanaka T. Epigenetic changes mediating transition to chronic kidney disease: Hypoxic memory. Acta Physiol (Oxford, England) 2018;222:4. doi: 10.1111/apha.13023.
Zoja C, Buelli S, Morigi M. Shiga toxin triggers endothelial and podocyte injury: The role of complement activation. Pediatr Nephrol 2017. doi: 10.1007/s00467-017-3850-x.
Meyer NJ, Reilly JP, Feng R, Christie JD, Hazen SL, Albert CJ, et al.
Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome. JCI Insight 2017;2. pii: 96432. doi: 10.1172/jci.insight.96432.
Eriguchi M, Lin M, Yamashita M, Zhao TV, Khan Z, Bernstein EA, et al.
Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy. Am J Physiol Renal Physiol 2018;314:F531-42. doi: 10.1152/ajprenal.00523.2017.
Piatti P, Monti LD. Insulin resistance, hyperleptinemia and endothelial dysfunction in coronary restenosis. Curr Opin Pharmacol 2005;5:160-4. doi: 10.1016/j.coph.2004.10.004.
Kipshidze N, Dangas G, Tsapenko M, Moses J, Leon MB, Kutryk M, et al.
Role of the endothelium in modulating neointimal formation: Vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J Am Coll Cardiol 2004;44:733-9. doi: 10.1016/j.jacc.2004.04.048.
Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, et al.
Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: Implications for cell-based vascular therapy. Circulation 2003;108:2710-5. doi: 10.1161/01.cir.0000096490.16596.a6.
Foteinos G, Hu Y, Xiao Q, Metzler B, Xu Q. Rapid endothelial turnover in atherosclerosis-prone areas coincides with stem cell repair in apolipoprotein E-deficient mice. Circulation 2008;117:1856-63. doi: 10.1161/circulationaha.107.746008.