Influence of Hypoxia Inducible Factor-1α of Endothelial Progenitor Cells on Left Ventricular Function in Experimental Myocardial Infarction

Based on the promotion of myocardial activity via endothelial progenitor cells (EPCs) subsequent to acute myocardial infarction (AMI), our research was designed to explore the influence of excessive HIF-1α expression in expanded EPCs (eEPCs) on promotion of the activity of left ventricle subsequent to MI. Isolation of EPCs from cord blood was performed before transduction with the help of retroviral vector with or without HIF-1α expression. Transplantation was performed subsequent to ligation of the left anterior descending coronary artery in mice. Ejection fraction (EF) of left ventricle was promoted via transplantation after 2 weeks. Excessive HIF-1α expression enhanced EF of left ventricle and decreased the extent of MI. It was revealed via functional studies that excessive HIF-1α expression enhanced proliferation of EPCs triggered by low oxygen concentration and suppressed cell death in the region of infarction. Moreover, markers of endothelium CD31, VEGF, and eNOS were upregulated. Transplantation of eEPCs with excessive HIF-1α expression in AMI can promote myocardial activities by increasing differentiation, generation of vessels, proliferation of eEPCs, and suppressing cell death. The above findings propose that regulation of EPCs via HIF-1α enhances the activity as well as mobilization of EPCs, indicating that reinforcement of expression of HIF-1α is beneficial for coronary heart disease.

Effects of adipose-derived stromal cells and endothelial progenitor cells on adipose transplant survival and angiogenesis

Background A paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear. Methods The EPCs-ASCs cocultures prepared in different ratios were subjected to tube formations assay to verify whether ASCs could directly participate in the tube genesis. The supernatant from cultured ASCs was used to stimulate EPCs to evaluate the effects on the angiogenic property of EPCs, as well as capacity for migration and invasion. A coculture model with transwell chamber were used to explore the regulation of angiogenesis markers expression in EPCs by ASCs. We then mixed ASCs with EPCs and transplanted them with adipose tissue into nude mice to evaluate the effects on angiogenesis in adipose tissue grafts. Results In the EPCs-ASCs cocultures, the tube formation was significantly decreased as the relative abundance of ASCs increased, while the ASCs was found to migrate and integrated into the agglomerates formed by EPCs. The supernatant from ASCs cultures promoted the migration and invasion of EPCs and the ability to form capillary-like structures. The expression of multiple angiogenesis markers in EPCs were significantly increased when cocultured with ASCs. In vivo, ASCs combined with EPC promoted vascularization in the fat transplant. Immunofluorescence straining of Edu and CD31 indicated that the Edu labeled EPC did not directly participate in the vascularization inside the fat tissue. Conclusions ADSC can participate in the tube formation of EPC although it cannot form canonical capillary structures. Meanwhile, Soluble factors secreted by ASCs promotes the angiogenic potential of EPCs. ASCs paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of angiogenesis markers in EPCs. The results of in vivo experiments showed that ASCs combined with EPCs significantly promote the formation of blood vessels in the fat implant. Remarkably, EPCs may promote angiogenesis by paracrine regulation of endogenous endothelial cells (ECs) rather than direct participation in the formation of blood vessels.

The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. Objectives: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. Conclusion: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term. Graphical abstract

Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions

The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.

Relationship Between Keloid Pathogenesis and Endothelial Progenitor Cells: A Review Study

Context: Keloid scars are disfiguring lesions (ie, reddish-brown bulges on the skin surface) formed after a minor injury or surgical invasion. They lead to severe itching or pain, thereby causing physical and psychological distress in patients. Evidence Acquisition: Scholarly databases, including Web of Science, PubMed, and Google Scholar, were searched for relevant articles using keywords such as “keloids,” “endothelial progenitor cells” (EPCs), and “CD34-positive cells.” Results: Keloid scars are classified as an intractable disease; their cause is unknown, and there is no specific therapy. Their pathogenic effects on inflammation around wounds and fibroblasts have been extensively studied. However, details regarding their onset mechanism and definitive factors that contribute to their formation have not yet been elucidated. Adult stem cell therapy, especially regenerative therapy aimed at recovering tissue structure and function, has been extensively studied globally. In our recently published study, we identified an association between keloid scar development and EPCs. However, there is still no systematic review in this regard. Conclusions: This paper provides information on preventing keloids and further understanding the cause of this disease by reviewing previous studies on the association between keloids and EPCs.

miRNA-130 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells Through PI3K/AKT/mTOR Pathways

<sec> <title>Aim:</title> In this study, we aimed to investigate the effects and mechanisms of miRNA-130a in human endothelial progenitor cells (EPCs) involved in Deep vein thrombosis (DVT). </sec> <sec> <title>Methods:</title> EPCs were isolated and identified by cell morphology and surface marker detection. The effect of miR-130a on the migration, invasion and angiogenesis of EPCs in vitro were also detected. In addition, whether miR-130a is involved in the MMP-1 expression and Akt/PI3K/mTOR signaling pathway was also demonstrated. </sec> <sec> <title>Results:</title> Results suggested that miRNA-130a promotes migration, invasion, and tube formation of EPCs by positively regulating the expression of MMP-1 through Akt/PI3K/mTOR signaling pathway. </sec> <sec> <title>Conclusion:</title> Thus, as a potential therapeutic target, miRNA-130a may play an important role in the treatment of DVT. </sec>