Die Bedeutung entzündlicher Reaktionen für die Pathogenese der Arteriosklerose
Untersuchungen an einem in vitro Modell menschlicher kardialer Endothelzellen
While the cellular mechanisms of atherosclerosis have been intensively studied, the mechanisms leading to preferential localization of atherosclerotic lesions are less well understood. To further define these mechanisms, endothelial cells from coronary arteries, i.e. vessels with frequent atherosclerotic lesions, were isolated and grown in vitro. In order to compare the reactions of both cell types, endothelial cells derived from microvessels of human hearts were isolated and cultured under identical conditions. Incubation of endothelial cells with oxidized LDL (75 µg/ml protein) induced a significant increase in PAI-1 activity (182 %, p<0.05) in coronary macrovascular endothelial cells. This stimulatory effect of ox-LDL was less significant in microvascular endothelial cells (144%, p<0,05). n-LDL did not influence secreted PAI-1 activity. Stimulation with angiotensin II induced expression of E-selectin more effectively in coronary macrovascular than in microvascular endothelial cells. In addition, angiotensin II-induced E-selectin expression led to increased E-selectin-dependent adhesion of HL60 cells to coronary macrovascular endothelial cells under flow conditions, while only little effects were observed with cardiac microvascular endothelial cells. In contrast, L-selectin-dependent adhesion, which has been shown to play an important role in inflammatory reactions, was preferentially observed in cardiac microvascular endothelial cells and could only be stimulated with TNF(, not by angiotensin II. Therefore, these cellular differences may in part explain specific properties of cardiac endothelial cells: Such that atherosclerotic lesions are localized in macrovascular vessel segments, whereas inflammatory responses are predominantly found in the microvasculature.
Document Full Text
School:Humboldt-Universität zu Berlin
Source Type:Master's Thesis
Keywords:E-Selectin L-Selectin oxidierte LDL endothelial cells oxidized
Date of Publication:07/17/2001