血管钙化（VC）是导致动脉粥样硬化（AS)斑块破裂的重要原因之一。研究表明，AS部位的炎症介质可诱导内皮细胞和血管平滑肌细胞（VSMCs）产生基质囊泡或凋亡小体，在促进AS斑块不稳定的同时，也参与了VC形成。我们前期研究发现，血小板激活后产生的微粒（PMPs）可促进单核细胞炎症介质的释放。同时，PMPs中含有与骨形成相关的miR-21、miR-223和骨钙素（OC）。因此我们推测，PMPs可能在促进VC中发挥重要作用。本项目拟研究PMPs与VSMCs的膜融合效应；探讨Ca2+、OC、miR-21和miR-223向VSMCs的转移，及其对VSMCs向成骨表型转化的调控作用和机制；并采用小鼠主动脉环体外培养模型，研究在高磷或无磷条件下，PMPs对VC的影响；体内实验研究PMPs促进apoE基因敲除小鼠VC形成的作用机制。旨在阐明PMPs促进VC的作用和机制，为血管钙化的防治提供新的策略和依据。

Vascular calcification is one of the main causes of atherosclerotic plaque rupture. Present studies have shown that inflammatory chemokines in the plaque induce endothelial cells and vascular smooth muscle cells (VSMCs) to release matrix vesicles or membrane niduses, and further to promote the calcification. We have found that platelet microparticles (PMPs) released by activated platelets can increase the secreation of inflammatory mediators by monocytes. PMPs also contain a lot of Ca2+, osteocalcin, miR-21 and miR-223, which are closely related to vascular calcification. The major assumption underlying this research is that PMPs may also play a crucial role in the accelerated formation of vascular calcification. The membrane fusion effect between PMPs and VSMCs will be studied using two-photon confocal microscopy and scanning electron microscopy. Using flow cytometry, qPCR and Western blot to evaluate the transfer of Ca2+, osteocalcin, miR-21 and miR-223 from PMPs into VSMCs. The osteogenic transition of VSMCs induced by PMPs, and the expression of the target genes in VSMCs regulated by miR-21 and miR-223, will be further studied. Mouse aortic ring organ calcification stimulated by PMPs in the condition of no or high-Pi will be studied.Animal experiments will be performed to study the promotion role and the mechanism of PMPs on vascular calcification in aorta of apoE gene knockout mice. All studies above should be very important for clarifying the mechanism of PMPs-promoted vascular calcification, and provide a novel strategy for the prevention of vascular calcification.