HDL诱导EPC-MVs释放miR-126对心肌细胞的保护作用研究

Our preliminary study found that EPC-microvesicles (MVs) can activate the PI3K/Akt/eNOS signaling pathway to against oxidative stress and to protect cardiomyocytes from hypertrophy and apoptosis induced by Ang II, which may be regulated by the miRNA carried by EPC-MVs. However, the mechanism of promoting the release of protective MVs from EPCs remains unexplored. Recent studies indicated HDL was an important factor to influence the quantity and function of EPCs, and can activate PI3K/AKT/eNOS pathway to reduce oxidative stress. Furthermore, another study showed that EPC-MVs exerted its protective effect via miR-126, and HDL-bound miR-126 was very rich. Accordingly, we assume that HDL may help in the process of promoting the release of miR-126 by EPC-MVs and activate PI3K/Akt/eNOS signaling pathway to inhibit oxidative stress. In the present proposal we would study the effect of HDL on the release of EPC-MVs, and then play the role of myocardial protection via miR-126 in vivo and in vitro. The outcomes of this project will provide a new strategy for reducing the cardiac remodeling by EPC-MVs.

我们前期研究发现EPCs来源的微囊泡（MVs）可以激活PI3K/Akt/eNOS信号通路抵抗AngⅡ诱导的氧化应激调节减少心肌肥大和凋亡，这些作用可能受MVs携带的miRNA调节，但促进EPCs释放保护性MVs的机制尚不明确。新近研究表明HDL是影响EPCs数量和功能的重要因素，并可激活PI3K/AKT/eNOS通路减少氧化应激；还有研究表明EPCs-MVs通过传递miR-126来发挥其保护作用，且HDL结合含量丰富的miR-126。据此，我们设想HDL通过促进EPC-MVs释放miR-126而激活PI3K/Akt/eNOS信号通路来抑制氧化应激。本项目拟从体内、外两个层面着重研究HDL对EPCs释放MVs的影响及其通过miR-126来发挥保护心肌的作用，为EPC-MVs成为心脏重构防治的新靶点提供更充分的科学依据。

本项目从体内、外两个层面研究了高密度脂蛋白（HDL）对内皮祖细胞（EPCs）释放微囊泡（MVs）的影响及其保护心肌的作用机制。研究发现HDL介导的EPC-MVs释放可通过所携带的RNA而激活PI3K/Akt/eNOS信号通路表达，从而进一步抑制AngII诱导的心肌细胞肥大和凋亡来发挥保护心肌的作用，为EPC-MVs成为心脏重构防治的新靶点提供科学依据。