Journal of Bioequivalence & Bioavailability

Angiotensin type 1 receptors regulate a specifi c set of micro RNA's in cardiovascular tissues including human arteries

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Soren P. Sheikh

Scientific Tracks Abstracts: JBB

Abstract:

T he Angiotensin II type 1 receptor (AT1R) is a key regulator of blood pressure and cardiac contractility and it is profoundly involved in development of cardiac disease as illustrated by the widespread use of AT1R blockers. Since several microRNAs (miRNAs) have been implicated in cardiac disease, we asked whether miRNAs might be regulated by AT1R signals in vitro using primary cardiac myocytes and fi broblasts and in vivo using aortas from rats with AngII induced hypertension and isolated arteries from patients with cardiovascular disease. We fi rst performed global miRNA microarray analysis of angiotensin II (Ang II) mediated miRNA regulation in HEK293N cells over-expressing the AT1R followed by verifi cation with quantitative PCR in HEK293N cells, cardiac myocytes and fi broblasts. Th ese experiments revealed several miRNAs (miRNA-7, miRNA-29b, miRNA-129-3p, miRNA-132, and miRNA-212) that were upregulated by Ang II. We next infused AngII in Wistar rats to investigate in vivo regulation. All candidate miRNA?s except miR-29b were also up-regulated in rat aortas aft er chronic AngII infusion. Strongly supporting diff erentially expressed candidate miRNA?s and securing human relevance, we extended these fi ndings to human arteries. Relevant candidate miRNA?s were measured in human arteries from 16 patients treated with and 16 not treated with AT1R blockers. Remarkably, we found a robust decrease in a set of miRNA?s including miR-7. We are currently examining target molecules in our diff erent experimental systems. Th e perspective is that the identifi ed miRNAs may be involved in Ang II-mediated cardiac biology and disease. Th is is important since modifi ed miRNA and anti-miRNA molecules have been reported to work directly as drugs opening novel pharmacological venues.