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, α-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 α-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.
Clinical Relevance
Thoracic aortic dissection is a catastrophic event involving the aorta. Our study has revealed that smooth muscle cell phenotypic switching in the aortic media is involved in extracellular matrix disorders and thus may impair the structure and the mechanical properties of the aortic wall and contribute to initiating dissection. Therefore, new therapeutic strategies for maintaining the contractile phenotype of aortic smooth muscle cells may be useful to prevent the formation of thoracic aortic dissection.
Cited by (0)
This work was supported by National Natural Science Foundation of China (grant number 81100224 to L.W.); Science and Technology Commission of Shanghai Municipality (grant number 08JC1404400 to Y.W.); and Graduate School of Fudan University (grant number 09111210050 to J.Z.).
Author conflict of interest: none.
Additional material for this article may be found online at www.jvascsurg.org.
The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.