Further characterization of the acetyl LDL (scavenger) receptor expressed by rabbit smooth muscle cells and fibroblasts.

Pitas, Robert E.; Friera, Annabelle M.; McGuire, Joseph; Dejager, S.

doi:10.1161/01.atv.12.11.1235

Cited by 43 publications

(32 citation statements)

References 33 publications

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“…Indeed, smooth muscle cells do take up lipoproteins, as we know now; remnant particles are taken up more avidly than are VLDLs, as shown by Bierman et al (18,19). Under the right conditions, smooth muscle cells can express scavenger receptors (20,21) and take up modified forms of LDL. Still, only a relatively small fraction of the foam cells in the early fatty streak lesion are derived from smooth muscle cells.…”

Section: Early Attempts To Define the Pathogenesis Of Atherosclerosismentioning

confidence: 90%

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia

Steinberg

2005

Journal of Lipid Research

120

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The thesis of this set of reviews is that substantial evidence for a causal relationship between hypercholesterolemia and atherosclerosis began to appear over 100 years ago and was already strong enough 40 years ago that it should have been persuasive. However, little or nothing was done about it, certainly not at the clinical level, until the 1990s. Even after the National Institutes of Health gave its blessings to treatment of hypercholesterolemia [after the 1984 Consensus Conference on Lowering Blood Cholesterol to Prevent Heart Disease (1)], practicing physicians paid little attention (2-4). In 1983, almost 50% of internists surveyed said they did not recommend any therapy, not even diet therapy, unless a cholesterol level was over 300 mg/dl! Over 40% of these internists recommended drug treatment only if the level was over 340; 27% said they never recommended drug treatment (3)! This history of the cholesterol controversy attempts to sort out the reasons it took so long to convince the profession and the public that correction of hypercholesterolemia should be a national public health goal.Part I of this series (5) dealt with the landmark work of Anitschkow (6), which strongly indicted hypercholesterolemia as a sufficient cause of experimental atherosclerosis, and with that of Gofman et al. (7), which strongly suggested that the same was true for the human disease and first demonstrated the complexity of lipoproteins. Part II dealt with the several early lines of evidence that linked blood cholesterol to coronary heart disease (CHD) in humans, including the early clinical trials showing that cholesterol lowering by diet modification could indeed reduce risk (8). Here in Part III, we deal with one of the underlying reasons for the early skepticism about the lipid hypothesis, and that was the absence, until the 1980s, of an accepted, detailed hypothesis for lesion development that mechanistically linked lipoproteins to the pathogenesis of CHD. THE IMPORTANCE OF UNDERSTANDING MECHANISM IN GAINING ACCEPTANCE OF A HYPOTHESISThe lack of a well-delineated hypothesis is not necessarily a barrier to the acceptance of new directions in medical practice. The classic example is John Snow's demonstration that the 1854 cholera epidemic in London was attributable to contaminants in the water. When he removed the handle from the Broad Street pump, the number of cases in the area served by that pump promptly began to wane. Exactly what was in the water that caused the cholera would not be demonstrated for more than a quarter of a century. Still, the results of Snow's intervention were so dramatic that no one questioned the cause-andeffect relationship even in the absence of an explicit hypothesis . However, when the causal linkage is less obvious, the absence of a plausible hypothesis can be a significant deterrent to action.

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Section: Early Attempts To Define the Pathogenesis Of Atherosclerosismentioning

confidence: 90%

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia

Steinberg

2005

Journal of Lipid Research

120

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“…Pitas and colleagues have shown that in vitro cultured human and rabbit smooth muscle cells express low levels of SR-A but that expression can be markedly induced by treatment with phorbol esters or platelet secretion products, resulting in lipid accumulation and foam cell formation. 25,26,47,48 Tumor necrosis factor-␣, interferon-␥, and human cytomegalovirus infection have also been shown to induce expression of SR-A by smooth muscle cells in vitro. 49,50 In contrast, several studies of SR-A expression in human and rabbit atherosclerotic lesions using immunohistochemical and in situ hybridization techniques have failed to show significant receptor expression.…”

Section: Discussionmentioning

confidence: 99%

“…With such techniques it has been shown that in vitro cultured endothelial and smooth muscle cells, in addition to macrophages, have scavenger receptor activity. [25][26][27][28] However, the recent cloning of several receptors with the ability to mediate uptake of modified LDL 29 -33 has meant that the nature of the receptors responsible for these activities is unclear. In this current study, we describe the generation and characterization of high-titer polyclonal antisera against the human SR-A protein by using SR-Adeficient mice.…”

mentioning

confidence: 99%

Analysis of Macrophage Scavenger Receptor (SR-A) Expression in Human Aortic Atherosclerotic Lesions

Gough

Greaves²,

Suzuki³

et al. 1999

ATVB

128

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Abstract-The class A scavenger receptors (SR-As) are trimeric, integral membrane glycoproteins that exhibit unusually broad ligand-binding properties. A number of studies have suggested that these receptors may play an important role in host defense and in many macrophage-associated pathological processes, including atherosclerosis and Alzheimer's disease. The study of the expression and function of these receptors in human disease has been hampered by the lack of suitable antibodies recognizing human SR-A. This has generated questions regarding the nature of receptors responsible for scavenger receptor activity detected in a variety of cell types, including monocytes, macrophages, smooth muscle cells, and endothelial cells. To address these questions, we have produced high-titer antisera recognizing human SR-A by using mice deficient for SR-A (SR-A Ϫ/Ϫ). We show that SR-A Ϫ/Ϫ mice produce a significantly higher-titer immune response than do wild-type (SR-A ϩ/ϩ) littermates, with antisera of the former having a broad species reactivity and recognizing SR-A from humans, mice, and rabbits. The antisera recognize both type I and II SR-A in a wide range of immunological techniques. Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages. We also establish that human

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“…isolated from atherosclerotic lesions, and proposed that these gene expressions may be related to the phenotypic conversion of vascular smooth muscle cells to foam cells in atheromatous lesions (4,9,(44)(45)(46)(47). Furthermore, recent studies have demonstrated that PDGF-BB induces scavenger receptor expression in normal medial smooth muscle cells through protein kinase C activation (9,44) and IFN-y suppresses scavenger receptor activity (33,34).…”

Section: Methodsmentioning

confidence: 99%

Induction of sustained expression of proto-oncogene c-fms by platelet-derived growth factor, epidermal growth factor, and basic fibroblast growth factor, and its suppression by interferon-gamma and macrophage colony-stimulating factor in human aortic medial smooth muscle cells.

Inaba

Gotoda²,

Harada³

et al. 1995

J. Clin. Invest.

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Vascular medial smooth muscle cells migrate, proliferate and transform to foam cells in the process of atherosclerosis. We have reported that the intimal smooth muscle cells express proto-oncogene c-fms, a characteristic gene of monocyte-macrophages, which is not normally expressed in medial smooth muscle cells. In the present study, we demonstrated that combinations of platelet-derived growth factor (PDGF)-BB and either epidermal growth factor (EGF) or fibroblast growth factor (FGF) induced high expression of c-fms in normal human medial smooth muscle cells to the level of intimal smooth muscle cells or monocyte-derived macrophages, whereas c-fins expression by PDGF-BB alone was 1/1o and both EGF and FGF had no independent effect Invest. 1995Invest. . 95:1133Invest. -1139

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Further characterization of the acetyl LDL (scavenger) receptor expressed by rabbit smooth muscle cells and fibroblasts.

Cited by 43 publications

References 33 publications

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia

Analysis of Macrophage Scavenger Receptor (SR-A) Expression in Human Aortic Atherosclerotic Lesions

Induction of sustained expression of proto-oncogene c-fms by platelet-derived growth factor, epidermal growth factor, and basic fibroblast growth factor, and its suppression by interferon-gamma and macrophage colony-stimulating factor in human aortic medial smooth muscle cells.

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