Effects on activated endothelial cells

Coordinator:		Dr. Kerstin Lehmann
Institution:		Charité-Berlin, Center for Cardiovascular Research (CCR)
Homepage:		www.ccr.charite.de/site

Patients with CKD face an elevated risk for atherosclerosis and CVD. This has been attributed in part to soluble uremic peptides/mediators which accumulate during CKD in the serum, leading to endothelial dysfunction and smooth muscle cell (SMC) phenotypic changes.

Therefore, we will examine the effects of
1) known uremic peptides/mediators and
2) the effects of plasma from uremic patients on endothelial function/plasticity by secretomic, proteomic and genomic ap-proaches.

This approach should allow to identify new soluble and cellular mediators, provoking endothelial damage, pathogenic vascular calcification, chronic inflammation and atherosclerosis.

In addition, effects of
(1) uremic mediators and
(2) serum of uremic patients on endothelial / monocyte adhesion, endothelial cell (EC) permeability, stress fibre formation, changes in adher-ens junction proteins and smooth muscle cell function will be analysed, to unravel responsible signalling pathways.

Since an important determinant of EC function/plasticity and integrity is hemodynamic blood flow, we will carry out all in vitro experiments on EC by employing a pulsatile flow model using a cone-plate viscometer.