Abstract 301: Angiotensin II-induced Aortic Stiffening is Associated With Upregulation of Mir-21 And Downregulation of Mir-29b
Background Arterial stiffening is associated with aging, as well as numerous diseases such as hypertension, congestive heart failure, diabetes mellitus and renal failure, and has been identified as an independent risk factor for cardiovascular disease. Consequently there is a growing interest in the mechanisms that govern the process of arterial remodeling. Recently, small noncoding RNAs, termed microRNAs (miRs), have emerged as powerful cellular regulators involved in disease and tissue remodeling. More specifically, miR-29b downregulation as well as miR-21 upregulation have been identified as pro-fibrotic mechanisms in various cardiovascular disease models. This study investigated the role of miR-21 and miR-29b in a mouse model of AngII-induced arterial remodeling.
Materials and methods Angiotensin II (AngII) (1000ng/kg/min) was infused via osmotic pumps in 10-week-old apoE-/- male mice (C57BL/6J background) for 7 days. Subsequently, arterial stiffness was determined in vivo using ultrasound-based measurements. Abdominal aortas were harvested and expression of various collagen isoforms (Col1a1, Col3a1, Col5a1) known to be crucial determinants of arterial remodeling/stiffening was quantified via qRT-PCR. We also measured expression levels of miR-21 and miR-29b.
Results AngII stimulation resulted in an increased aortic stiffness paralleled by a marked pro-fibrotic response as evidenced by significant increases in Col1a1, Col3a1, and Col5a1 in the infrarenal aorta compared to baseline levels (p < 0.05). This increase was accompanied by significant downregulation of miR-29b, and upregulation of miR-21 (p <0.05).
Conclusion The pro-fibrotic response in AngII-mediated arterial remodeling is associated with an increase in miR-21 and a decrease in miR-29b. Modulation of miR-21 and miR-29b have both been successful in altering fibrotic mechanisms in various cardiovascular diseases. These data suggest they may also be potential targets in the treatment of hypertensive vascular remodeling/arterial stiffening.
- © 2013 by American Heart Association, Inc.