Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus
Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. C J Schwartz , A J Valente , E A Sprague , J L Kelley , A J Cayatte and M M Rozek Department of Pathology, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio 78284-7750. Abstra...
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Published in | Diabetes care Vol. 15; no. 9; pp. 1156 - 1167 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.09.1992
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Subjects | |
Online Access | Get full text |
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Summary: | Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus.
C J Schwartz ,
A J Valente ,
E A Sprague ,
J L Kelley ,
A J Cayatte and
M M Rozek
Department of Pathology, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio 78284-7750.
Abstract
In this review, we have highlighted pivotal cellular and molecular events in the initiation and progression of atherosclerosis.
Key components of lesion initiation are an enhanced focal intimal influx and accumulation of lipoproteins, including LDL in
hemodynamically determined lesion-prone areas, focal monocyte-macrophage recruitment, intimal generation of ROS, and oxidative
modification of lipoproteins (including LDL [Ox-LDL]). Modified lipoproteins are taken up by the non-downregulating macrophage
scavenger receptor, with foam cell formation and the development of the so-called fatty streak. One transitional event in
lesion progression is foam cell necrosis, likely attributable to the cytotoxicity of both intimal free radicals and Ox-LDL,
with development of an extracellular metabolically inert lipid core. Another is the migration to and proliferation within
the intima of medial SMCs, leading to the synthesis of plaque collagens, elastin, and proteoglycans. Mural thrombosis plays
a significant role in the late-stage progression of lesions. Regression of lesions is considered a function of the dynamic
balance among components of initiation, progression, plaque stabilization, and removal of plaque constituents--the so-called
regression quartet. Here, we critically examine how components of diabetes mellitus might impact not only lesion development,
but also lesion regression. It is concluded that some components of diabetes mellitus augment key mechanisms in lesion initiation
and progression and will likely retard the processes of plaque regression. Specifically, we focus on the various influences
of diabetes mellitus on lipoprotein influx and accumulation, free radical generation and Ox-LDL, monocyte-macrophage recruitment,
thrombosis and impaired fibrinolysis, and the reverse cholesterol transport system. The importance of nonenzymatic protein
glycosylation in modifying a number of these processes is emphasized. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 0149-5992 1935-5548 |
DOI: | 10.2337/diacare.15.9.1156 |