Calcification and Vascular Cell Differentiation

描述（由申请人提供）：血管钙化与心血管疾病（CVD）死亡率高度相关，尤其是在终末期肾病（ESRD）和糖尿病患者中。除了在心脏瓣膜病、钙化耐受和特发性婴儿动脉钙化中观察到的不适当的生物矿化的破坏性影响之外，血管钙化现在被认为是动脉粥样硬化斑块负荷的标志物，也是动脉顺应性丧失和随年龄、糖尿病和肾功能不全而观察到的脉压增加的主要原因。血管钙化是否会引起或加重动脉粥样硬化尚不清楚，将在本提案中讨论。此外，动脉壁细胞似乎在介导血管钙化中发挥特别重要的作用，特别是在观察到骨软骨组织的情况下，例如在与ESRD相关的动脉粥样硬化和中膜钙化中。该提案旨在确定参与骨软骨组织形成的细胞的起源，以及控制其分化的机制。这些研究将有助于开发新的治疗策略，以预防和潜在逆转血管钙化，这是ESRD人群的迫切需求。

DESCRIPTION (provided by applicant): Vascular calcification is highly correlated with cardiovascular disease (CVD) mortality, especially in end stage renal disease (ESRD) and diabetic patients. In addition to the devastating effects of inappropriate biomineralization seen in cardiac valvulopathies, calciphylaxis and idiopathic infantile arterial calcification, vascular calcification is now recognized as a marker of atherosclerotic plaque burden as well as a major contributor to loss of arterial compliance and increased pulse pressure seen with age, diabetes and renal insufficiency. Whether or not vascular calcification can cause or exacerbate atherosclerosis is not known, and will be addressed in this proposal. Furthermore, arterial wall cells appear to play a particularly important role in mediating vascular calcification, especially in situations where osteochondral tissue is observed, such as in atherosclerosis and medial calcification associated with ESRD. This proposal seeks to identify the origins of the cells participating in osteochondral tissue formation, and mechanisms controlling their differentiation. These studies will aid in the development of novel therapeutic strategies to prevent and potentially reverse vascular calcification, an urgent need in the ESRD population.