Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.

Rosenfeld, Michael; Tsukada, Toyohiro; Gown, Allen M.; Ross, Russell

doi:10.1161/01.atv.7.1.9

Cited by 304 publications

(112 citation statements)

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“…This observation was further confirmed on Watanabe heritable hyperlipemic rabbits (WHHL) and cholesterol-fed rabbits 29,30,31 and in intimal thickening of human aorta. 32,33 Although the exact location and the mechanism(s) of MRL formation are not completely understood, one can safely assume that the process may take place either on LDL interaction with ECs, or during transcytosis or within the subendothelial space by extended interaction with matrix components and cells.…”

Section: Transcytosed Lipoproteins Amass Within the Subendothelium Assupporting

confidence: 57%

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

Simionescu¹

2007

ATVB

224

152

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Abstract-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 ␤-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.

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Section: Transcytosed Lipoproteins Amass Within the Subendothelium Assupporting

confidence: 57%

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

Simionescu¹

2007

ATVB

224

152

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“…Adhesion of circulating monocytes to the endothelium and consequent reduction in their rolling are important components in the atherogenic process (Cybulsky and Gimbrone, 1991;Gimbrone et al, 1995;Rosenfeld et al, 1987). Experiments and numerical simulations demonstrate that formation of membrane tethers reduces the force exerted on specific bonds (i.e.…”

Section: Discussionmentioning

confidence: 99%

The effect of cellular cholesterol on membrane-cytoskeleton adhesion

Sun

Northup

Marga

et al. 2007

Journal of Cell Science

167

161

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Whereas recent studies suggest that cholesterol plays important role in the regulation of membrane proteins, its effect on the interaction of the cell membrane with the underlying cytoskeleton is not well understood. Here, we investigated this by measuring the forces needed to extract nanotubes (tethers) from the plasma membrane, using atomic force microscopy. The magnitude of these forces provided a direct measure of cell stiffness, cell membrane effective surface viscosity and association with the underlying cytoskeleton. Furthermore, we measured the lateral diffusion constant of a lipid analog DiIC12, using fluorescence recovery after photobleaching, which offers additional information on the organization of the membrane. We found that cholesterol depletion significantly increased the adhesion energy between the membrane and the cytoskeleton and decreased the membrane diffusion constant. An increase in cellular cholesterol to a level higher than that in control cells led to a decrease in the adhesion energy and the membrane surface viscosity. Disassembly of the actin network abrogated all the observed effects, suggesting that cholesterol affects the mechanical properties of a cell through the underlying cytoskeleton. The results of these quantitative studies may help to better understand the biomechanical processes accompanying the development of atherosclerosis.

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“…Although much convincing evidence demonstrates the importance of blood-borne monocytes in early lesion development, 1,5,6 the potential contribution of resident macrophages has been more difficult to assess. Experiments involving injection of labeled tracer monocytes can provide estimates for the rate of recruitment of circulating inflammatory cells but do not directly address the issue of mobilization of macrophages already present in arterial tissue.…”

mentioning

confidence: 99%

Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

Lessner

Prado

Waller

et al. 2002

The American Journal of Pathology

152

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Macrophage-derived foam cells in developing atherosclerotic lesions may potentially originate either from recruitment of circulating monocytes or from migration of resident tissue macrophages. In this study, we have determined the source of intimal macrophages in the apoE-knockout mouse flow-cessation/hypercholesterolemia model of atherosclerosis using a bone marrow transplantation approach. We also examined the time course and spatial distribution of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression to assess whether endothelial adhesion molecules were involved in recruitment of either circulating monocytes or resident macrophages. We used allelic variants of the mouse common leukocyte antigen (CD45) to distinguish host-derived and donor-derived white blood cells (WBCs) both in blood and in macrophage-rich carotid lesions. We found that the distribution of CD45 isoforms in lesions is similar to that of circulating WBCs, whereas the host-type CD45 isoform is more prevalent in resident adventitial macrophages. These data indicate that macrophage-derived foam cells in the lesion derive mainly from circulating precursors rather than from resident macrophages. The corresponding time course of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression suggests that recruitment of circulating WBCs by endothelial adhesion molecules is likely to be more important during lesion initiation than during the later phase of rapid lesion growth. Both in experimental models of atherosclerosis and in human disease, infiltration of macrophages into the arterial intima constitutes one of the earliest cellular events in the development of atherosclerotic lesions. 1-3 Macrophages in the lesion may be derived either from cells already resident in the arterial wall 4 or from circulating monocytes that have undergone diapedesis. Because the mechanisms of cellular recruitment and/or activation are likely to differ depending on the source of the inflammatory cells, determining the relative contribution to lesion growth of cells from these two sources may have important implications in devising successful strategies to slow the growth of lesions.Although much convincing evidence demonstrates the importance of blood-borne monocytes in early lesion development, 1,5,6 the potential contribution of resident macrophages has been more difficult to assess. Experiments involving injection of labeled tracer monocytes can provide estimates for the rate of recruitment of circulating inflammatory cells but do not directly address the issue of mobilization of macrophages already present in arterial tissue. Moreover, alterations in adhesion molecule expression that can occur during monocyte isolation and labeling may modify the interaction between circulating monocytes and the vascular wall. The recent development of a polymerase chain reaction-based method of quantifying monocyte recruitment has shown promise of improved sensitivity and ease of quantitation compared to more traditional approach...

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Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.

Cited by 304 publications

References 0 publications

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

The effect of cellular cholesterol on membrane-cytoskeleton adhesion

Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

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