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The pathogenesis of atherosclerosis: atherogenesis and inflammation.
Lab Invest. 1988 Mar; 58(3):249-61.LI

Abstract

Current concepts of the pathogenesis of atherosclerosis have been reviewed, emphasizing some of the similarities of the mechanisms and events involved to those in inflammation. Figure 2 is a schematic summary of these events. Hyperlipidemia, or some component of hyperlipidemic serum, as well as other risk factors, are thought to cause endothelial injury, resulting in adhesion of platelets and/or monocytes and release of PDGF (and other growth factors), which leads to smooth muscle migration and proliferation. It is clear that endothelial injury need not be denuding, and in fact may consist of altered endothelial function (dysfunction); adhesion of monocytes, increased permeability of endothelium, and disturbances in growth control can occur without morphologically obvious endothelial injury. Hyperlipidemia, hypertension, smoking, immune injury, and other risk factors may contribute to this endothelial dysfunction in different ways and sometimes in combination. Smooth muscle cells produce large amounts of collagen, elastin, and proteoglycans and these form part of the atheromatous plaque. Hyperlipidemia contributes in a number of ways (as discussed earlier), and indeed, in the severely hypercholesterolemic patient, such as one with familial hypercholesterolemia, is alone sufficient to cause atherosclerosis in the absence of other risk factors. Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from insudation from the lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque should be viewed as reflecting imbalance between influx and efflux, and it is possible that high-density lipoprotein is the molecule which helps clear the cholesterol from these accumulations (134). The diagram (right) also depicts the possibility that smooth muscle proliferation may occur without endothelial injury at all. There are several postulated mechanisms for such an occurrence: loss of growth control, direct smooth muscle injury (such as by LDL), and autonomous proliferation by the mechanisms suggested by Benditt. The theoretical scheme presented is based largely on in vitro work, only partly substantiated by experimental and human studies, and does not explain the precise mechanisms by which all risk factors increase the susceptibility to atherosclerosis.(

ABSTRACT

TRUNCATED AT 400 WORDS)

Authors+Show Affiliations

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

3279259

Citation

Munro, J M., and R S. Cotran. "The Pathogenesis of Atherosclerosis: Atherogenesis and Inflammation." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 58, no. 3, 1988, pp. 249-61.
Munro JM, Cotran RS. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest. 1988;58(3):249-61.
Munro, J. M., & Cotran, R. S. (1988). The pathogenesis of atherosclerosis: atherogenesis and inflammation. Laboratory Investigation; a Journal of Technical Methods and Pathology, 58(3), 249-61.
Munro JM, Cotran RS. The Pathogenesis of Atherosclerosis: Atherogenesis and Inflammation. Lab Invest. 1988;58(3):249-61. PubMed PMID: 3279259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pathogenesis of atherosclerosis: atherogenesis and inflammation. AU - Munro,J M, AU - Cotran,R S, PY - 1988/3/1/pubmed PY - 1988/3/1/medline PY - 1988/3/1/entrez SP - 249 EP - 61 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab. Invest. VL - 58 IS - 3 N2 - Current concepts of the pathogenesis of atherosclerosis have been reviewed, emphasizing some of the similarities of the mechanisms and events involved to those in inflammation. Figure 2 is a schematic summary of these events. Hyperlipidemia, or some component of hyperlipidemic serum, as well as other risk factors, are thought to cause endothelial injury, resulting in adhesion of platelets and/or monocytes and release of PDGF (and other growth factors), which leads to smooth muscle migration and proliferation. It is clear that endothelial injury need not be denuding, and in fact may consist of altered endothelial function (dysfunction); adhesion of monocytes, increased permeability of endothelium, and disturbances in growth control can occur without morphologically obvious endothelial injury. Hyperlipidemia, hypertension, smoking, immune injury, and other risk factors may contribute to this endothelial dysfunction in different ways and sometimes in combination. Smooth muscle cells produce large amounts of collagen, elastin, and proteoglycans and these form part of the atheromatous plaque. Hyperlipidemia contributes in a number of ways (as discussed earlier), and indeed, in the severely hypercholesterolemic patient, such as one with familial hypercholesterolemia, is alone sufficient to cause atherosclerosis in the absence of other risk factors. Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from insudation from the lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque should be viewed as reflecting imbalance between influx and efflux, and it is possible that high-density lipoprotein is the molecule which helps clear the cholesterol from these accumulations (134). The diagram (right) also depicts the possibility that smooth muscle proliferation may occur without endothelial injury at all. There are several postulated mechanisms for such an occurrence: loss of growth control, direct smooth muscle injury (such as by LDL), and autonomous proliferation by the mechanisms suggested by Benditt. The theoretical scheme presented is based largely on in vitro work, only partly substantiated by experimental and human studies, and does not explain the precise mechanisms by which all risk factors increase the susceptibility to atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS) SN - 0023-6837 UR - https://www.unboundmedicine.com/medline/citation/3279259/The_pathogenesis_of_atherosclerosis:_atherogenesis_and_inflammation_ L2 - https://ClinicalTrials.gov/search/term=3279259 [PUBMED-IDS] DB - PRIME DP - Unbound Medicine ER -