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The effects of diet on occlusive coronary artery atherosclerosis and myocardial infarction in scavenger receptor class B, type 1/low-density lipoprotein receptor double knockout mice.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2014 Nov; Vol. 34 (11), pp. 2394-403. Date of Electronic Publication: 2014 Sep 11. - Publication Year :
- 2014
-
Abstract
- Objective: Deficiency of the high-density lipoprotein receptor, scavenger receptor class B, type I (SR-BI), in apolipoprotein E knockout or hypomorphic mice, respectively, results in spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis, myocardial infarction, and early death. Here, we examine effects of SR-BI deficiency on cardiovascular phenotypes in low-density lipoprotein receptor (LDLR) knockout mice fed different atherogenic diets.<br />Approach and Results: SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6C(hi) and Ly6C(int) monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice.<br />Conclusions: Diet-accelerated atherosclerosis and occlusive, platelet-rich CA disease in SR-BI/LDLR double knockout mice is affected by amounts of cholesterol and cholate in atherogenic diets and is accompanied by increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CAs and increased Ly6C(hi) and Ly6C(int) monocytes in circulation. The increased vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CA endothelial cells in SR-BI-deficient mice likely explains their increased susceptibility to atherosclerosis in CAs.<br /> (© 2014 American Heart Association, Inc.)
- Subjects :
- Animals
Arterial Occlusive Diseases metabolism
Cholates adverse effects
Cholesterol, Dietary adverse effects
Coronary Artery Disease metabolism
Cytokines blood
Disease Models, Animal
Endothelium, Vascular metabolism
Incidence
Intercellular Adhesion Molecule-1 metabolism
Mice
Mice, Knockout
Myocardial Infarction metabolism
Receptors, LDL genetics
Risk Factors
Scavenger Receptors, Class B genetics
Vascular Cell Adhesion Molecule-1 metabolism
Arterial Occlusive Diseases epidemiology
Coronary Artery Disease epidemiology
Diet, Atherogenic adverse effects
Myocardial Infarction epidemiology
Receptors, LDL deficiency
Scavenger Receptors, Class B deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 34
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 25212235
- Full Text :
- https://doi.org/10.1161/ATVBAHA.114.304200