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Báo cáo y học: "Systemic vasculopathy with altered vasoreactivity in a transgenic mouse model of scleroderma"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Systemic vasculopathy with altered vasoreactivity in a transgenic mouse model of scleroderma. | Derrett-Smith et al. Arthritis Research Therapy 2010 12 R69 http arthritis-research.eom content 12 2 R69 RESEARCH ARTICLE Open Access Systemic vasculopathy with altered vasoreactivity in a transgenic mouse model of scleroderma Emma C Derrett-Smith Audrey Dooley Korsa Khan Xu Shi-wen David Abraham and Christopher P Denton Abstract Introduction Vasculopathy including altered vasoreactivity and abnormal large vessel biomechanics is a hallmark of systemic sclerosis SSc . However the pathogenic link with other aspects of the disease is less clear. To assess the potential role of transforming growth factor beta TGF-P overactivity in driving these cardiovascular abnormalities we studied a novel transgenic mouse model characterized by ligand-dependent activation of TGF-P signaling in fibroblasts. Methods The transgenic mouse strain TP RIIAk-fib is characterized by balanced ligand-dependent upregulation of TGF-P signaling. Aortic and cardiac tissues were examined with histologic biochemical and isolated organ bath studies. Vascular and perivascular architecture was examined by hematoxylin and eosin H E and special stains including immunostaining for TGF-P1 and phospho-Smad2 3 pSmad2 3 . Confirmatory aortic smooth muscle cell proliferation phenotype and functional assays including signaling responses to exogenous TGF-P and endothelin-1 were performed. Aortic ring contractile responses to direct and receptor-mediated stimulation were assessed. Results Aortic ring contractility and relaxation were diminished compared with wild-type controls and this was associated with aortic adventitial fibrosis confirmed histologically and with Sircol assay. TGF-P1 and pSmad 2 3 expression was increased in the adventitia and smooth muscle layer of the aorta. Aortic smooth muscle cells from transgenic animals showed significant upregulation of TGF-P- responsive genes important for cytoskeletal function such as transgelin and smoothelin which were then resistant to further stimulation with .