转化生长因子-β在心脏重构中作用的研究进展

The study progression of transforming growth factor-β signaling in cardiac remodeling

由于对心肌、心肌间质细胞及免疫细胞的影响，转化生长因子-β（TGF—β）在心脏重构和心肌纤维化过程中发挥关键作用。小鼠心肌TGF—β过表达与心肌纤维化和心脏扩大相关。内源性TGF—β在心脏纤维化和肥厚重构过程中具有关键作用，且对超负荷心脏基质新陈代谢具有调整作用。在梗塞心肌中，TGF—β可以灭活炎症巨噬细胞，同时通过信号转导分子3（SMAD3）依赖途径促进肌纤维母细胞分化转移及基质合成。因此，TGF—β可能是梗塞由“炎症阶段”向“疤痕形成阶段”转变的“总开关”。TGF—β在心脏重构过程中具有决定性作用，有望成为心衰患者的治疗靶点。

Through transforming growth factor-β（TGF-β） effects on cardiomyocytes, mesenchymal and immune cells, plays an important role in the pathogenesis of cardiac remodeling and fibrosis. TGF- β overexpression in the mouse heart is associated with fibrosis and hypertrophy. Endogenous TGF-β plays a critical role in the pathogenesis of cardiac fibrotic and hypertrophic remodeling, and modulates matrix metabolism in the pressure-overloaded heart. In the infarcted heart, TGF-β deactivates inflammatory macrophages, while promoting myofibroblast transdifferentiation and matrix synthesis through Smad3-dependent pathways. Thus, TGF-β may serve as the ＂master switch＂ for the transition of the infarct from the inflammatory phase to formation of the scar. Because of its crucial role in cardiac remodeling, the TGF-β system may be a promising therapeutic target for patients with heart failure.