Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during development and pathological processes in vivo and during cell culture in vitro. Our previous studies demonstrated that retrovirally mediated expression of the versican V3 splice variant (V3) by ASMCs retards cell proliferation and migration in vitro and reduces neointimal thickening and macrophage and lipid accumulation in animal models of @entity1317 and @entity731 . However, the molecular pathways induced by V3 expression that are responsible for these changes are not yet clear. In this study, we employed a microarray approach to examine how expression of V3 induced changes in gene expression and the molecular pathways in @entity35 ASMCs. We found that forced expression of V3 by ASMCs affected expression of 521 genes by more than 1.5-fold. Gene ontology analysis showed that components of the extracellular matrix were the most significantly affected by V3 expression. In addition, genes regulating the formation of the cytoskeleton, which also serve as markers of contractile smooth muscle cells (SMCs), were significantly up-regulated. In contrast, components of the complement system, chemokines, chemokine receptors, and transcription factors crucial for regulating inflammatory processes were among the genes most down-regulated. Consistently, we found that the level of myocardin, a key transcription factor promoting contractile @entity9976 phenotype, was greatly increased, and the proinflammatory transcription factors @entity4026 and CCAAT/enhancer-binding protein b were significantly attenuated in V3-expressing SMCs. Overall, these findings demonstrate that V3 expression reprograms ASMCs promoting differentiated and anti-inflammatory phenotypes.

Expression of V3 Versican by XXXX Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes.

@entity9976 :: ('MESH:C564589', 'Disease') :: ['SMC'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity1317 :: ('MESH:D057772', 'Disease') :: ['vascular injury'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity4026 :: ('81736(Tax:10116)', 'Gene') :: ['NFkB1']
@entity35 :: (10116,Species) :: ['Rat']
