Abstract
Aging endothelial progenitor cells (EPCs) exhibit functional impairment in terms of proliferation, migration and survival. SIRT1 plays an important role in improving EPCs function. MeCP2, another important epigenetic regulator, is involved in regulating many life-related activities such as cell growth, death and senescence. Here we aim to explore the effect of MeCP2 on the functional activities of senescent EPCs and the underlying mechanisms. By using western blot and real-time PCR, we found that the expression levels of MeCP2 were up-regulated and SIRT1 were down-regulated with replicative senescence and H2O2-induced senescence. Through transduction with adenoviral vectors, EPCs overexpressing MeCP2 had significantly reduced EPCs function, and silencing MeCP2 improved EPCs function. In addition, the protein and mRNA levels of SIRT1 were decreased with MeCP2 overexpression and increased with MeCP2 knockdown. Through co-transfection of EPCs with MeCP2 and SIRT1, we observed that SIRT1 could reverse the effects of MeCP2 on EPCs. In summary, our work demonstrated that MeCP2 inhibited SIRT1 in senescent EPCs.
Highlights
In aging, endothelial dysfunction is a prominent health issue that eventually progresses to atherosclerosis and other vascular diseases [1]
In this study, based on our previous research results and sufficient reference support, we proposed that MeCP2 could induce the dysfunction of Endothelial progenitor cells (EPCs) in aging through repressing the expression of SIRT1
We found that the proliferation of EPCs was significantly reduced by MeCP2 overexpression and elevated by MeCP2 knockdown (Figure 7A)
Summary
Endothelial dysfunction is a prominent health issue that eventually progresses to atherosclerosis and other vascular diseases [1]. Endothelial progenitor cells (EPCs) are proposed to have the ability to repair injured endothelium cells by replacing damaged or dead endothelial cells [2,3,4]. Experiments in animal models verified that EPCs can repair impaired endothelial cells and improve angiogenesis and tissue perfusion in ischemia [5, 6]. Senescent EPCs usually experience function failure [8]. Age and age-related diseases may accelerate and aggravate EPC dysfunction, leading to limitations in the repair capacity of autologous EPCs’ [3, 11,12,13]. It seems crucial to clarify the mechanism underlying aging
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