The role of the cation channel TRPC6 in vascular remodeling

心血管疾病是工业化国家如联邦共和国德国的主要死因。在许多情况下，基础是动脉粥样硬化，例如外周动脉闭塞性疾病、冠心病或脑血管疾病。改善这些疾病的症状和预后的一个重要工具是血运重建，可以通过手术或介入进行。然而，在血管医学的所有领域中的介入手术的缺点是继发于球囊扩张或支架植入的血管的重新变窄（再狭窄）。今天的标准是植入药物涂层支架。这些释放抗增殖物质，主要是雷帕霉素衍生物，如西罗莫司或依维莫司。这些物质非特异性地抑制细胞增殖，这可以降低再狭窄率。通过对金属丝介导的内皮剥脱后血管蛋白质组的探索性研究，我们确定TRPC 6是一个有前途的治疗靶点。在这个项目中，我们现在希望进一步研究TRPC 6表达细胞参与血管重塑的分子，细胞和遗传基础，并首次了解治疗益处。

Cardiovascular diseases are the main cause of death in industrialized nations such as the Federal Republic of Germany. In many cases, the basis is atherosclerosis, e.g. in peripheral arterial occlusive disease, coronary heart disease or cerebrovascular diseases. An essential tool for improving the symptoms and often also the prognosis in these diseases is revascularization, which can be carried out either surgically or interventionally. A disadvantage of interventional procedures in all areas of vascular medicine, however, is the renewed narrowing (restenosis) of the vessels secondary to balloon dilatation or stent implantation. Today's standard is the implantation of drug-coated stents. These release antiproliferative substances, mostly rapamycin derivatives such as sirolimus or everolimus. Cell proliferation is unspecifically inhibited by these substances, which could reduce the restenosis rate. Using an exploratory study of the vascular proteome after wire-mediated endothelial denudation, we identified TRPC6 as a promising therapeutic target. In this project we now want to further investigate the molecular, cellular and genetic basis of the involvement of TRPC6-expressing cells in vascular remodeling and gain first insights into a therapeutic benefit.