Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions.

Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions. Am J Physiol Heart Circ Physiol. 2017 Mar 10;:ajpheart.00029.2017 Authors: Durgin BG, Cherepanova OA, Gomez D, Karaoli T, Alencar GF, Butcher JT, Zhou YQ, Bendeck MP, Isakson BE, Owens GK, Connelly JJ Abstract Atherosclerotic plaque rupture with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke. Although smooth muscle cells (SMC) produce and respond to collagens in vitro, there is no direct evidence in vivo that SMC are a crucial source of collagens and that this impacts lesion development or fibrous cap formation. We sought to determine how conditional SMC specific knockout of collagen type XV (COL15A1) in SMC lineage tracing mice affects advanced lesion formation given: 1) we previously identified a Col15a1 sequence variant associated with age related atherosclerosis; 2) COL15A1 is a matrix organizer enhancing tissue structural integrity; and 3) siRNA mediated Col15a1 knockdown increased migration and decreased proliferation of cultured human SMC. We hypothesized that SMC-derived COL15A1 is critical in advanced lesions, specifically in fibrous cap formation. Surprisingly, we demonstrate that SMC specific Col15a1 knockout mice fed a Western diet for 18 weeks failed to form advanced lesions. SMC specific Col15a1 knockout resulted in lesions reduced in size by 78%...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research