MiR‐mediated regulation of coronary collateral growth in the metabolic syndrome

Abstract

In response to transient, repetitive coronary artery occlusion, native collateral vessels enlarge. We stimulate coronary collateral growth (CCG) in the rat model by transient, repetitive LAD occlusion. CCG is impaired in the metabolic syndrome, both in the human and in the rat model (JCR). We evaluated CCG by measurements of coronary blood flow (microspheres). We hypothesized that lack of CCG in the JCR rat is in part due to aberrant phenotypic modulation of vascular smooth muscle cells (VSMCs). VSMC phenotype is regulated by transcription factors myocardin and Klf‐4, which are regulated by microRNA (miR)‐145. We hypothesized that decreased miR‐145 in the JCR rat leads a less contractile VSMC phenotype resulting in an inability to form functional collaterals. Our results show that expression of VSMC‐specific contractile proteins, myocardin, and miR‐145 are decreased in the JCR rat heart while Klf‐4 is increased in the later stages of CCG versus normal rats. These findings suggest that decreased miR‐145 expression in the metabolic syndrome correlates with a less contractile VSMC phenotype which may account for impaired CCG. Support: RO1HL093052 and AHA11PRE7690011.