血管平滑肌细胞凋亡小体在血管钙化中的作用研究

Vascular calcification is a pathological condition that occurs in the pathologic processes of a series of diseases, including atherosclerosis. Atherosclerotic calcification resembles osteogenesis in several aspects. The matrix vesicles were known to be critical for mineralization in bone formation. Recent studies have shown that vascular calcification is a regulated process similar to bone formation. Matrix vesicle-like structures have also been found in calcified arteries, these structures were derived from vascular smooth muscle cells and contained BAX protein, a proapoptotic member of the bcl-2 family, indicating that may be remanats of apoptotic cells.Recent studies have shown that apoptotic bodies from human vascular smooth muscle cells can initiate calcification in vitro. However, the vascular smooth muscle cells. Vascular smooth muscle cells, well known to have phenotypic heterogeneity in vivo. The mechanism underlying the apoptotic bodies undergo calcification from different phenotypes and pathological stage is not known. Our initial studies showed that the apoptotic bodies derived from different differentiative stage have different roles in vascular calcification. Therefore, In the present work, we have investigated the different effect between vascular smooth muscle cells apoptotic bodies(SMC AB) and calcified vascular smooth muscle cells apoptotic bodies(CVC AB) by chemical kinetics in vitro . In addition, the structural and functional characteristics of CVC AB and SMC AB were investigated. We now try to uncover the mechanisms by the biological and chemical methods from the medical chemistry.

血管钙化作为一种病理过程存在于多种疾病发生发展过程中，动脉粥样硬化是其中的一种。研究表明，动脉粥样硬化血管钙化的发生机制类似于骨形成。在骨形成中基质小泡的作用非常关键。近年来的研究显示在血管钙化过程中也存在类似基质小泡样的结构。这些结构因含有凋亡蛋白家族bcl-2中的BAX蛋白，而被认为是细胞凋亡的产物凋亡小体。血管平滑肌细胞凋亡小体可以启动钙化的研究已有报道，但血管平滑肌细胞作为一种多表型、多亚型的细胞群体，在不同的病理阶段及不同表型下其凋亡小体诱导和启动钙化的作用是否一致，具体机理尚不明确。我们的初步研究显示，不同分化阶段的平滑肌细胞凋亡小体在血管钙化过程中的作用存在差异。有鉴于此，我们从医化学的角度出发，选择了正常平滑肌细胞和类成骨样平滑肌细胞作为研究对象，应用化学方法比较研究两种凋亡小体的体外钙化动力学及终产物的组成和性质的差别，并试图用生物学和化学的研究分析方法，探讨其发生机理。