Abstract 408: Severity of Hypertension does not Correlate with Increased miR-221 and miR-222 Expression

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Multiple smooth muscle microRNA (miR) are required for normal regulation of blood pressure. miR-221 and miR-222 promote vascular remodeling through down regulation of the cyclin-dependent kinase inhibitor, p27Kip1. The vasculature of the spontaneously hypertensive rat (SHR) exhibits reduced expression of p27Kip1 that promotes vascular remodeling. Internal mammary arteries (IMAs) of diabetic subjects undergoing coronary artery bypass grafting exhibit elevated levels of miR-221 and miR-222. Given the relationship between diabetes and hypertension and the fact that the SHR exhibit low levels of p27Kip1, we hypothesized that increasing severity of hypertension would correlate with an increase in miR-221 and miR-222 in the vasculature that promotes vascular remodeling. Using multivariate linear regression, we evaluated the levels of miR-221 and miR-222 in the IMAs of both diabetic (n=19) and non-diabetic (n=18) subjects with reference to systolic and diastolic blood pressure, number of anti-hypertensive medications, and whether hypertension was controlled. Additionally, we tested whether individual anti-hypertension medication classes correlated with changes in miR-221 and miR-222 levels. When corrected for the presence of diabetes, none of these parameters correlated with a change in miR-221 and miR-222 levels. These data suggest both that miR-221 and miR-222 are not among the smooth muscle miRs involved in the regulation of blood pressure, and that hypertension does not promote vascular remodeling through changes in miR-221 and miR-222.

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