Severe hyperlipidemia causes impaired renin–angiotensin system function in apolipoprotein E deficient mice

Dyslipidemia is a known risk factor for cardiovascular diseases and may associate with renal injury. Using mouse models with various degrees of hypercholesterolemia and hypertryliceridemia, we investigated the effects of lipids on the renin–angiotensin system (RAS). ApoE −/− mice were fed either a h...

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Bibliographic Details
Published in:Atherosclerosis 2006-05, Vol.186 (1), p.86-91
Main Authors: Mazzolai, Lucia, Korber, Martine, Bouzourene, Karima, Aubert, Jean-François, Nussberger, Jürg, Stamenkovic, Ivan, Hayoz, Daniel
Format: Article
Language:English
Subjects:
Animals
ApoE −/ − mice
Apolipoproteins E - deficiency
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure
Cardiology. Vascular system
Cardiovascular system
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
Hyperlipidemias - blood
Hyperlipidemias - complications
Hyperlipidemias - pathology
Hypertension, Renal - blood
Hypertension, Renal - etiology
Hypertension, Renal - physiopathology
Immunohistochemistry
Kidney - pathology
Lymphatic system
Medical sciences
Mice
Mice, Inbred C57BL
Pharmacology. Drug treatments
Prognosis
Renin
Renin - blood
Renin-Angiotensin System - physiology
Risk Factors
Two-kidney one clip
Vasodilator agents. Cerebral vasodilators
Vertebrates: cardiovascular system
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Summary:Dyslipidemia is a known risk factor for cardiovascular diseases and may associate with renal injury. Using mouse models with various degrees of hypercholesterolemia and hypertryliceridemia, we investigated the effects of lipids on the renin–angiotensin system (RAS). ApoE −/− mice were fed either a high fat diet (HF-ApoE −/−; mice developed hypertriglyceridemia and severe hypercholesterolemia) or regular chow (R-ApoE −/−; mice developed less severe hypercholesterolemia only). Renal histopathology in the HF-ApoE −/− revealed massive lipid accumulation especially at the glomerular vascular pole. In these mice plasma renin concentration was significantly reduced (489 ± 111 ng/(ml h) versus 1023 ± 90 ng/(ml h) in R-ApoE −/−mice) and blood pressure was consequently significantly lower than in R-ApoE −/− (104 ± 2 mmHg versus 115 ± 2 mmHg, respectively). A model of renin-dependent renovascular hypertension (two-kidney, one clip) was generated and HF-ApoE −/− mice proved unable to increase renin secretion, and blood pressure, in response to diminished renal perfusion as compared to regular chow fed mice (665 ± 90 ng/(ml h) versus 2393 ± 372 ng/(ml h), respectively and 106 ± 3 mmHg versus 140 ± 2 mmHg, respectively). Hypertriglyceridemia and severe hypercholesterolemia are associated with renal lipid deposition and impaired renin secretion in ApoE −/− mice exposed to high fat diet. These observations further characterize the phenotype of this widely used mouse model and provide a rationale for the use of these mice to study lipid induced organ damage.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2005.07.017