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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. 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. 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. These modulations of TIMPs, VEGF and ER-α expression induced by RSV may act as local stimulating factors for arteriolar growth in the myocardium. © 2014 S. Karger AG, Basel.


Anwar J Siddiqui, Thomas Gustafsson, Christer Sylven, Milita Crisby. Rosuvastatin inhibits TIMP-2 and promotes myocardial angiogenesis. Pharmacology. 2014;93(3-4):178-84

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PMID: 24854110

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