191 Role of mir-214 in angiotensin ii induced hypertensive heart disease

Background Cardiac dysfunction is one of the hallmarks of hypertension. It is characterised by cardiac fibrosis, diastolic dysfunction and development of heart failure. The mechanisms of hypertensive heart disease are not fully understood. Recent studies suggest a role of miR-214 in regulation of fibrosis. Thus, the aim of this work is to investigate the role miR-214 has in the cardiac sequelae of hypertension. Methods Hypertension was induced in three month old miR-214 knock out (KO) and wild type (WT) littermates using 490 ng/kg/min angiotensin II (Ang II) for 14 or 28 days (n=4–6). Blood pressure was monitored by tail cuff plethysmography. Cardiac fibrosis was assessed by picrosirius red and Massons trichrome staining. Mir214 expression was assessed by Taqman and in situ hybridisation (ISH). Cardiac function was assessed by echocardiography. Effects of Ang II on fibrosis genes was studied in primary cardiac fibroblasts. Results 14 day Ang II infusion caused 4-fold induction of miR-214 in the left ventricle of C57bl/6 mice (p COL1A1 mRNA compared with their WT littermates (p in vivo observations, in vitro fibroblast studies show that KO fibroblasts showed significantly reduced induction of COL1A1 (p COL3A1 (p Conclusions Cardiac fibrosis, hypertrophy and diastolic dysfunction are enhanced in miR-214 KO animals. The mechanisms of this observation are not caused by mir214 effects in cardiac fibroblasts, but through other mechanisms that need to be further addressed.