MicroRNA-145 Targeted Therapy Reduces Atherosclerosis

• DOI: 10.1161/circulationaha.111.084186
• Publication Date: 2012-09-10T20:34:09Z
• Authors: Fina Lovren; Yi Pan; Adrian Quan; Krishna K. Singh; Praphulla C. Shukla; Nandini Gupta; Brent M. Steer; Alistair J. Ingram; Milan Gupta; Mohammed Al-Omran; Hwee Teoh; Philip A. Marsden; Subodh Verma
• Keywords: Myocardin; Calponin; KLF4; Apolipoprotein E; Fibrous cap

MicroRNA are essential posttranscriptional modulators of gene expression implicated in various chronic diseases. Because microRNA-145 is highly expressed vascular smooth muscle cells (VSMC) and regulates VSMC fate plasticity, we hypothesized that it may be a novel regulator atherosclerosis plaque stability.Apolipoprotein E knockout mice (ApoE(-/-)) were treated with either lentivirus under the control cell (SMC)-specific promoter SM22α or before commencing Western diet for 12 weeks. The SMC-targeted treatment markedly reduced size aortic sinuses, ascending aortas, brachiocephalic arteries. It also significantly increased fibrous cap area, necrotic core collagen content. Cellular composition analyses revealed less macrophages ApoE(-/-) SMC-specific microRNA-145. These demonstrated marked increases calponin levels α-smooth actin-positive SMC areas their atherosclerotic lesions. Furthermore, lentiviral delivery resulted KLF4 elevated myocardin aortas from mice, consistent an effect to promote contractile phenotype VSMC.VSMC-specific overexpression vivo therapeutic target limit morphology cellular composition, shifting balance toward stability vs rupture.