Atrial Natriuretic Peptide - a regulatory protein in endothelial activation. Characterization of its in vivo anti-inflammatory action and the molecular targets involved

内源性心血管多肽ANP(Inn：Carperiide，HANP®)和BNP(Inn：nesiritie，Natrecor®)是治疗急性心力衰竭的新药。大量的体外研究表明，ANP影响内皮细胞激活和炎症过程中的重要信号通路。本研究旨在探讨心钠素作为血管内皮细胞激活调节蛋白的体内相关性。因此，无论是外源性给药的作用，还是内源性产生的ANP的作用，都会引起人们的兴趣。因此，第一部分的工作将集中在ANP对内皮细胞激活的影响以及ANP对内毒素(LPS)处理的小鼠白细胞-内皮细胞相互作用的影响。将特别关注负责的信号级联和主要目标分子，如磷酸酶MKP-1。在项目的第二部分，内源性ANP/NPR/cGMP-系统的作用将通过各自的转基因动物在脂多糖诱导的炎症中得到表征。综上所述，本研究旨在找出心钠素是否是体内内皮细胞激活和炎症的调节蛋白，并试图阐明其潜在的分子机制。

The endogenous cardiovascular peptides ANP (INN: carperitide, HANP®) and BNP (INN: nesiritide, Natrecor®) are novel drugs for the treatment of acute heart failure. A substantial amount of in vitro work indicates that ANP affects important signalling pathways involved in endothelial cell activation and inflammation. This proposal aims to investigate the in vivo relevance of ANP as a regulator protein in endothelial cell activation. Thereby, both the role of exogenously administered, as well as endogenously produced ANP will be of interest. Consequently, the first part of the work will focus on the effect of ANP on endothelial activation as well as the influence of ANP on leukocyte-endothelium interactions in mice treated with lipopolysaccharide (LPS). Special attention will be given to the responsible signalling cascades and major target molecules such as the phosphatase MKP-1. In the second part of the project, the role of the endogenous ANP/NPR/cGMP-system will be characterized in LPS-induced inflammation by use of respective transgenic animals. In summary the proposed work aims to find out whether ANP is a regulatory protein in endothelial cell activation and inflammation in vivo and attempts to elucidate the underlying molecular mechanisms.