Transcriptome profiling reveals that the SM22α-regulated molecular pathways contribute to vascular pathology

摘要: Smooth muscle cell marker, SM22α, was down-regulated in the pathogenesis of arterial diseases including atherosclerosis, restenosis and abdominal aortic aneurysms. However, question still exists whether this down-regulation actively contributes to vascular diseases. In an ongoing effort understand role here we explored transcriptome profiling by RNA-Seq from arteries SM22α(-/-) SM22α(+/+) mice. Analysis revealed that most enriched pathways caused SM22α-knockout were hematopoiesis, inflammation lipid metabolism, respectively, NF-κB, RXRα PPARα major upstream regulators. The candidate genes involved metabolism clustered atherosclerosis. Thus suspected molecular basis mice already prepared for initiation Further analysis suggested up-regulated TNF NF-κB pathway activation. Our results showed loss SM22α exacerbated TNF-α-mediated activation increased expression levels ApoCI vitro, while overexpression suppressed addition, disruption enhanced injury-induced neointimal hyperplasia, molecules related with cellular adhesion extracellular matrix degradation. Taken together, these findings not only can contribute atherosclerosis basis, but also further confirmed cells may become more sensitive stimulation, increasing its tendency develop Meanwhile, rescuing provide a novel therapeutic strategy