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, 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.
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, 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.
Authors: Selda Sherifova; Gerhard Sommer; Christian Viertler; Peter Regitnig; Thomas Caranasos; Margaret Anne Smith; Boyce E Griffith; Ray W Ogden; Gerhard A Holzapfel Journal: Acta Biomater Date: 2019-08-26 Impact factor: 8.947
Authors: Guangxin Li; Mo Wang; Alexander W Caulk; Nicholas A Cilfone; Sharvari Gujja; Lingfeng Qin; Pei-Yu Chen; Zehua Chen; Sameh Yousef; Yang Jiao; Changshun He; Bo Jiang; Arina Korneva; Matthew R Bersi; Guilin Wang; Xinran Liu; Sameet Mehta; Arnar Geirsson; Jeffrey R Gulcher; Thomas W Chittenden; Michael Simons; Jay D Humphrey; George Tellides Journal: J Clin Invest Date: 2020-03-02 Impact factor: 14.808
Authors: Andrés I Rodríguez; Gábor Csányi; Daniel J Ranayhossaini; Douglas M Feck; Kory J Blose; Lillian Assatourian; David A Vorp; Patrick J Pagano Journal: Arterioscler Thromb Vasc Biol Date: 2014-12-30 Impact factor: 8.311
Authors: Emanuela Branchetti; Paolo Poggio; Rachana Sainger; Eric Shang; Juan B Grau; Benjamin M Jackson; Eric K Lai; Michael S Parmacek; Robert C Gorman; Joseph H Gorman; Joseph E Bavaria; Giovanni Ferrari Journal: Cardiovasc Res Date: 2013-08-28 Impact factor: 10.787