Elastin-elastase-atherosclerosis revisited.
This review proposes reinvestigation of a topic studied in the author's laboratory over the last decades concerning the age-dependent modifications of the vascular extracellular matrix (ECM) as related to atherogenesis and its recognized risk-factors: blood lipids, lipoproteins. Most salient previous results are confronted with recent publications in this field. Age-dependent modifications of the vascular wall discussed in this review include upregulation of elastolytic enzymes, demonstrated for the first time in the vascular wall in this laboratory, matrix biosynthesis and receptor function. The progressive deposition of lipids in elastic tissues as well as the addition of lipoproteins or lipids to cell and organ cultures were shown to modify matrix biosynthesis and upregulate elastase expression. Lipid-elastin interactions exhibit a great deal of specificity as shown by the nature and amount of lipids accumulating in elastin in vivo and in vitro. Recent epidemiological studies (the EVA study) enables the confrontation of blood lipid parameters with matrix related components (serum elastase and inhibitors, elastin peptides, fibronectin) in the same blood samples. The elastin laminin receptor present on vascular cells was shown to trigger NO dependent vasodilation, and downregulation of cholesterol synthesis. Both of these functions decrease or disappear with age except the upregulation of elastase release which is preserved and increased. Recent experiments extended these findings to T-lymphocytes present also in the atherosclerotic plaque. Finally several recent publications are analyzed which give more precision on the cellular mechanisms underlying the above-described modifications.
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Université Paris 6, Centre de Recherche Bioclinique sur le Vieillissement, Groupe Hospitalier Charles Foix-Jean Rostand, Ivry sur Seine, France. 106517.545@compuserve.com
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Jacotot
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D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000096:biosynthesis; D004549:Elastin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000378:metabolism*; D011817:Rabbits; D012307:Risk Factors; D014664:Vasodilation
D004549:Elastin; D002784:Cholesterol; D010196:Pancreatic Elastase