Key result
In LDLR KO mice fed a high cholesterol diet, administration of rosuvastatin or amlodipine reduced the overexpression of LOX-1 and AT1R genes and ameliorated cardiomyocyte hypertrophy and fibrosis.
Why the study?
Does rosuvastatin or amlodipine reduce cardiomyocyte hypertrophy and collagen deposition in low-density lipoprotein receptor knockout (LDLR KO) mice fed a high cholesterol diet?
Does rosuvastatin or amlodipine reduce cardiomyocyte hypertrophy and collagen deposition in low-density lipoprotein receptor knockout (LDLR KO) mice fed a high cholesterol diet?
Answers are grounded in this paper and cite their sources.
In a hypercholesterolemic mouse model, rosuvastatin and amlodipine ameliorated cardiac hypertrophy and fibrosis independent of blood pressure changes, potentially by reducing oxidant stress signaling.
Hypercholesterolemia is a common accompaniment of atherosclerosis and may be associated with cardiac hypertrophy. To define the mechanistic basis of cardiac hypertrophy in hypercholesterolemia, we fed low-density lipoprotein receptor knockout (LDLR KO) mice regular diet or high cholesterol (HC) diet for 26 weeks. There was clear evidence of cardiomyocyte hypertrophy and collagen deposition in the hearts of LDLR KO mice fed with HC diet, confirmed by histopathology (hematoxylin and eosin and Picrosirius staining) and upregulation of genes for brain natriuretic peptide, alpha-tubulin, transforming growth factor beta1, and connective tissue growth factor (CTGF). These changes were independent of change in blood pressure. The hypercholesterolemic mice hearts showed an upregulation of LOX-1, an oxidized low-density lipoprotein receptor, and angiotensin II type 1 receptor (AT1R) at messenger RNA level. In addition, there was a marked upregulation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nuclear factor kappaB (NF-kappaB) messenger RNA, indicating overexpression of markers of oxidant stress. A separate group of LDLR KO mice were fed HC diet along with a potent 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor rosuvastatin or a dihydropyridine calcium channel blocker amlodipine. Administration of rosuvastatin or amlodipine reduced the overexpression of genes for LOX-1 and AT1R and associated NADPH oxidase and NF-kappaB. These phenomena were associated with a marked decrease in cardiomyocyte hypertrophy and collagen deposits in and around the cardiomyocytes. In conclusion, this study provides evidence of cardiac hypertrophy and fibrosis in hypercholesterolemia independent of blood pressure change LOX-1 and AT1R act as possible signals for oxidant stress leading to alterations in cardiac structure during hypercholesterolemia. Most importantly, rosuvastatin and amlodipine ameliorate cardiomyocyte hypertrophy and fibrosis.
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Kang et al. (2009) studied Hypercholesterolemia and cardiac hypertrophy. Rosuvastatin or amlodipine vs. High cholesterol diet alone was evaluated on Cardiomyocyte hypertrophy, collagen deposition, and gene expression (LOX-1, AT1R, NADPH oxidase, NF-kappaB). In LDLR KO mice fed a high cholesterol diet, administration of rosuvastatin or amlodipine reduced the overexpression of LOX-1 and AT1R genes and ameliorated cardiomyocyte hypertrophy and fibrosis.
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