Key result
Rosuvastatin inhibited TIMP-1 and TIMP-2 expression and enhanced myocardial VEGF-A and ER-α expression independently of plasma lipid changes in ApoE knockout mice.
Why the study?
Does rosuvastatin modulate the expression of angiogenic factors in the myocardium of ApoE-/- mice on a high cholesterol diet?
Does rosuvastatin modulate the expression of angiogenic factors in the myocardium of ApoE-/- mice on a high cholesterol diet?
Rosuvastatin modulates TIMPs, VEGF, and ER-α expression in the myocardium, suggesting a mechanism for promoting local arteriolar growth independent of its lipid-lowering effects.
May promote myocardial arteriogenesis via TIMP/VEGF modulation in hyperlipidemic mice; leaves open human translation.
BACKGROUND: Angiogenesis is usually driven by inflammation. Matrix metalloproteinases MMP-3 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 are implicated in vascular remodeling. TIMP-2 exhibits antiangiogenic properties. Statins show benefits that are additional to lipid lowering including pro- and antiangiogenic properties. Atherosclerotic lesions in the coronary arteries have been well studied, but less is known about the fine terminal branches of the myocardial vasculature. METHODS: To examine this, we studied rosuvastatin (RSV) treatment in ApoE knockout (ApoE(-/-)) mice fed a high cholesterol (HC) diet. Hearts from ApoE(-/-) mice on a normal diet, HC diet and HC diet with RSV were harvested to determine MMP-3, MMP-9, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF)-A and estrogen receptor-α (ER-α) mRNA. RESULTS: RSV inhibited TIMP-1 and TIMP-2 expression and enhanced myocardial VEGF-A and ER-α expression, independently of plasma lipid level changes, but had no effect on MMP-3 and MMP-9 expression. CONCLUSIONS: These modulations of TIMPs, VEGF and ER-α expression induced by RSV may act as local stimulating factors for arteriolar growth in the myocardium.
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Siddiqui et al. (2014) studied Atherosclerosis / Hypercholesterolemia. Rosuvastatin vs. Normal diet and high cholesterol diet without rosuvastatin was evaluated on Expression of MMP-3, MMP-9, TIMP-1, TIMP-2, VEGF-A and ER-α mRNA. Rosuvastatin inhibited TIMP-1 and TIMP-2 expression and enhanced myocardial VEGF-A and ER-α expression independently of plasma lipid changes in ApoE knockout mice.
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