e34 Arterioscler Thromb Vasc Biol May 2016 shown that homocysteine can induce the senescence of endothelial and progenitor cells via telomerase inactivation and length shortening. 24 The underlying mechanism behind this was revealed to be cross talk between CCCTC-binding factor and SP1, which contributed to homocysteine-induced human telomerase reverse transcriptase (hTERT) DNA methylation. 24 Recent microRNA studies reveal a significant role for these short noncoding RNA in vascular regeneration through influence on stem/progenitor cell functions. 25, 26 MicroRNA-31 (miR-31) and miR-720 were found to be expressed at lower levels in circulating endothelial progenitor cells of patients with coronary artery disease. 27 The pathways regulating miR-31, miR-720, and vasohibin were found to be critical for the activation of endothelial progenitor cells, and their absence resulted in coronary artery disease. The circulating concentrations of miR-31, miR-720, and vasohibin could present promising prognosis biomarkers for cardiovascular diseases. 27 In another study, miR-22 was found to be markedly upregulated during smooth muscle cell differentiation from stem/progenitor cells with the great reduction of methyl CpG–binding protein 2. 28 It was also found that miR-27b expression was decreased in bone marrow–derived angiogenic cells. 23 Treatment with a miR-27b mimetic improved bone marrow–derived angiogenic cell function, including proliferation, adhesion, tube formation, and delayed apoptosis, but did not affect migration. Elevated thrombospondin-1 protein in angiogenesis was suppressed on transfection with a miR-27b mimic. miR-27b improved topical cell therapy of diabetic skin wound closure. Normal bone marrow–derived angiogenic cell therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. All of these discoveries above could be potential approaches of therapies of vascular regeneration. 23 Inflammatory cytokines are crucial for the development of vascular diseases, and their influence on stem/progenitor cells has recently been emphasized. 29 Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine 12 (CXCL12), which binds to receptor CXCR4, is a potent chemotactic to many types of cells, including endothelial progenitor cells. 30, 31 It was believed to act as a novel suppressor of endothelial permeability by activating the CXCR4/phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/Ras-related C3 botulinum toxin substrate 1 (RAC1) signaling pathway in endothelial cells. 32 Specific deletion of endothelial CXCR4 in a CRE mouse model led to a reduction in number of Sca-1+Flk1+CD31+ endothelial progenitor cells in the circulation with enhanced neointima formation 3 weeks after guidewire injury, indicating that CXCR4 is crucial for efficient reendothelialization. 33 However, a clinical study involving 3359 participants with 9.3 years of follow up revealed that SDF-1 was associated with heart failure and all-cause mortality but not with coronary artery disease or myocardial infarction. 34 It is well known that the cytokine transforming growth factor-α (TNF-α), released by macrophages, induces the endothelial inflammatory response by inducing expression of adhesion molecules. 35 A novel finding of the effect of TNF-α released by macrophages on stem/progenitor cells has recently been reported. 36 It was demonstrated that TNF-α-mediated stem cell differentiation toward endothelial lineages was driven by direct binding of nuclear factor-κB (p65) to specific vascular …