Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, De Boelelaan 1117, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, the Netherlands.
Department of Cell and Chemical Biology, Leiden UMC, 2300 RC Leiden, the Netherlands.
Pharmacol Ther. 2023 Apr;244:108389. doi: 10.1016/j.pharmthera.2023.108389. Epub 2023 Mar 20.
Right ventricular fibrosis is a stress response, predominantly mediated by cardiac fibroblasts. This cell population is sensitive to increased levels of pro-inflammatory cytokines, pro-fibrotic growth factors and mechanical stimulation. Activation of fibroblasts results in the induction of various molecular signaling pathways, most notably the mitogen-activated protein kinase cassettes, leading to increased synthesis and remodeling of the extracellular matrix. While fibrosis confers structural protection in response to damage induced by ischemia or (pressure and volume) overload, it simultaneously contributes to increased myocardial stiffness and right ventricular dysfunction. Here, we review state-of-the-art knowledge of the development of right ventricular fibrosis in response to pressure overload and provide an overview of all published preclinical and clinical studies in which right ventricular fibrosis was targeted to improve cardiac function.
右心室纤维化是一种应激反应，主要由心肌成纤维细胞介导。这种细胞群体对促炎细胞因子、促纤维化生长因子和机械刺激的水平升高敏感。成纤维细胞的激活导致各种分子信号通路的诱导，特别是有丝分裂原激活的蛋白激酶盒，导致细胞外基质的合成和重塑增加。虽然纤维化在响应缺血或（压力和容量）过载引起的损伤时提供结构保护，但它同时导致心肌僵硬和右心室功能障碍增加。在这里，我们综述了压力超负荷引起的右心室纤维化发展的最新知识，并概述了所有已发表的靶向右心室纤维化以改善心功能的临床前和临床研究。
