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