Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection
Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection
复制标题
胸主动脉夹层平滑肌细胞表型与细胞外基质紊乱的关联
DOI：
10.1016/j.jvs.2012.05.084
复制
发表时间：
2012-12-01
影响因子：
4.3
通讯作者：
Wang, Yuqi
中科院分区：
文献类型：
--
作者：
Wang, Lixin;Zhang, Jing;Wang, Yuqi
Objective: Extracellular matrix dysregulation in the aortic media has been considered as the intrinsic factor for the formation of thoracic aortic dissection. However, the mechanisms of extracellular matrix disorders in the dissected aortic media remain unclear. This study was designed to investigate the relevance between smooth muscle cell phenotypes and extracellular matrix disorders in the dissected media. Their interaction may account for the pathogenesis of thoracic aortic dissection.Methods and Results: Thoracic aortic samples were collected from 10 patients with thoracic aortic dissection and 10 controls. Primary cultures of aortic medial smooth muscle cells were obtained with optimized explant technique. In this study, alpha-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were applied as the contractile phenotypic markers and osteopontin was applied as the synthetic marker. Compared with controls, immunostaining and immunoblotting demonstrated that in vivo expression of alpha-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were significantly decreased in the dissected media, whereas that of osteopontin was elevated (P < .01 for all). In vitro expression of the phenotypic markers showed the similar patterns. Furthermore, smooth muscle cells derived from the dissected media exhibited enhanced proliferation (P < .01), increased collagens I and III synthesis (2.6- and 4.4-fold, respectively; P < .01 for both), and elevated matrix metalloproteinase-2 production (4.2-fold; P < .01). Consistently, the protein levels of type I and III collagens and matrix metalloproteinase-2 in the dissected media were raised by 4.6-, 4.0-, and 3.7-fold, respectively (P < .01 for all). Collagen deposition was correspondingly increased and elastic fibers were decreased and disrupted.Conclusions: Smooth muscle cells in the dissected media exhibit phenotypic switching from the contractile to the synthetic type. The synthetic smooth muscle cells increase collagen synthesis and matrix metalloproteinase-2 production, both of which can promote collagen deposition and elastin degradation in thoracic aortic dissection. (J Vasc Surg 2012;56:1698-709.)
