Published online before print November 30, 2006, doi: 10.1161/01.ATV.0000253884.13901.e4
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© 2007 American Heart Association, Inc.
Brief Review |
Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease
From the Institute of Cellular Biology and Pathology "Nicolae Simionescu," Bucharest, Romania.
Correspondence to Maya Simionescu, Institute of Cellular Biology and Pathology "Nicolae Simionescu, 8, B. P. Hasdeu Street, Bucharest, Romania. E-mail maya.simionescu{at}icbp.ro
By location, between the blood and tissues and the multiple functions, the endothelial cells (ECs) play a major role in securing body homeostasis. The ECs sense all variations occurring in the plasma and interstitial fluid, and respond (function of intensity), initially by modulation of their constitutive functions, then by dysfunction, expressed by temporarily altered functions and a phenotypic shift, and ultimately by injury/death. In dyslipidemia/hyperglycemia, the initial response of EC is the modulation of 2 constitutive functions: permeability and biosynthesis. Increased transcytosis of plasma ß-lipoproteins leads to their accumulation within the hyperplasic basal lamina, interaction with matrix proteins, and conversion to modified and reassembled lipoproteins (MRL). This generates a multipart inflammatory process and EC dysfunction characterized by expression of new cell adhesion molecules and MCP-1 that trigger T-lymphocytes and monocyte recruitment, diapedesis, and homing within the subendothelium where activated macrophages become foam cells. The latter, together with the subendothelial accrual of MRL, growth factors, cytokines, and chemokines, and accretion of smooth muscle cells of various sources lead to atheroma formation; in advanced disease, the EC overlaying atheroma take up lipids, become EC-derived foam cells, and the cytotoxic ambient ultimately conducts to EC apoptosis. Understanding the mechanisms of EC dysfunction is a prerequisite for EC-targeted therapy to reduce the incidence of cardiovascular diseases.
The initial key events in atherosclerosis are the dyslipidemia-induced subtle modulation of endothelial constitutive functions and the subendothelial progressive accumulation of modified and reassembled lipoproteins that trigger an inflammatory reaction manifested by the expression of endothelial cell adhesion molecules and intimal accrual of macrophages, smooth muscle cells, and inflammatory molecules.
Key Words: atherosclerosis • cardiovascular disease • dysfunction • endothelial cell • hyperglycemia • hyperlipemia • oxidative stress
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