Synergistic effects of cyclic tension and transforming growth factor-β1 on the aortic valve myofibroblast
Synergistic effects of cyclic tension and transforming growth factor-β1 on the aortic valve myofibroblast
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DOI：
10.1016/j.carpath.2007.03.006
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发表时间：
2007-09-01
影响因子：
3.7
通讯作者：
Sacks, Michael S.
中科院分区：
文献类型：
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作者：
Merryman, W. David;Lukoff, Howard D.;Sacks, Michael S.
背景资料：表型上，主动脉瓣间质细胞是动态肌成纤维细胞，在发育、疾病和重塑时表现出收缩性和激活性。表型调节的确切机制尚不清楚，但据推测，生物力学和生物化学因素都有影响。因此，我们假设单独和联合治疗的周期性张力和转化生长因子β 1将改变表型和随后的胶原蛋白生物合成的主动脉瓣间质细胞在原位。方法与结果：猪主动脉瓣瓣叶接受7天和14天的15%周期性拉伸（张力）; 0.5 ng/ml转化生长因子-β 1（TGF）; 15%周期性拉伸和0.5 ng/ml转化生长因子-β 1（张力+TGF），或无机械或细胞因子刺激（TGF）处理。将组织均质化并测定主动脉瓣间质细胞表型（平滑肌α-肌动蛋白）和胶原蛋白生物合成（通过热休克蛋白47，其进一步用I型胶原蛋白C-末端前肽验证）。在第7天和第14天，平滑肌α-肌动蛋白、搏动休克蛋白47和I型胶原C-末端前肽的量显著增加（P
Background: Phenotypically, aortic valve interstitial cells are dynamic myofibroblasts, appearing contractile and activated in times of development, disease, and remodeling. The precise mechanism of phenotypic modulation is unclear, but it is speculated that both biomechanical and biochemical factors are influential. Therefore, we hypothesized that isolated and combined treatments of cyclic tension and transforming growth factor-beta 1 would alter the phenotype and subsequent collagen biosynthesis of aortic valve interstitial cells in situ. Methods and results: Porcine aortic valve leaflets received 7- and 14-day treatments of 15% cyclic stretch (Tension); 0.5 ng/ml transforming growth factor-beta 1 (TGF); 15% cyclic stretch and 0.5 ng/ml transforming growth factor-beta 1 (Tension+TGF), or neither mechanical nor cytokine stimuli (Null). Tissues were homogenized and assayed for aortic valve interstitial cell phenotype (smooth muscle a-actin) and collagen biosynthesis (via heat shock protein 47, which was further verified with type I collagen C-terminal propeptide). At both 7 and 14 days, smooth muscle alpha-actin, beat shock protein 47, and type I collagen C-terminal propeptide quantities were significantly greater (P