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Proatherogenic flow conditions initiate endothelial apoptosis via thrombospondin-1 and the integrin-associated protein.

Abstract：

:Recently it has been shown that vascular endothelial cells (EC) are completely devoid of apoptosis if cultivated under a steady laminar flow and that apoptosis is induced by turning off the flow. An autocrine loop of thrombospondin-1 (TSP-1) and the alpha(v)beta(3) integrin/integrin-associated protein (IAP) complex has been identified as the molecular coupling device between flow and apoptosis. Lack of blood flow is a rare and mostly transient phenomenon whereas irregular flow conditions are permanently present at arterial bifurcations and sites of abnormal vessel morphology. Irregular flow conditions are established here either by the action of a cone-and-plate type flow apparatus generating a uniform turbulent flow or in a flow chamber by insertion of a local hindrance creating a zone of unsteady laminar flow with vortex formation and lowered shear stress. In both cases apoptosis is induced either throughout the entire monolayer or restricted to the locally defined area. Flow disturbance and apoptosis are coupled by the described autocrine loop of TSP-1 and the integrin/IAP receptor complex. In vivo atherosclerotic lesions occur predominantly at sites of flow irregularities, which are thought to be pro-atherogenic. Thus we propose a key role of the identified mechanosensitive apoptosis induction for the initiation of atherosclerosis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Freyberg MA,Kaiser D,Graf R,Buttenbender J,Friedl P

doi

10.1006/bbrc.2001.5314

subject

Has Abstract

pub_date

2001-08-10 00:00:00

pages

141-9

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(01)95314-8

journal_volume

286

pub_type

杂志文章

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