Daskalopoulos Evangelos P, Hermans Kevin C M, Blankesteijn W Matthijs
Department of Pharmacology, CARIM, Maastricht University, 50 Universiteitssingel, 6229ER Maastricht, P.O. Box 616, 6200MD Maastricht, The Netherlands.
Curr Pharm Des. 2014;20(12):1987-2002. doi: 10.2174/13816128113199990452.
Following myocardial infarction (MI), a dynamic and complex process called wound healing is initiated, aiming to produce a robust scar and limit adverse remodeling of the left ventricle (LV). Cardiac fibroblasts (CFs) - the most populous cardiac cell-type - differentiate into myofibroblasts under the influence of post-MI mechanical stress, transforming growth factor β (TGF-β) and various inflammatory signals. Myofibroblasts are contractile cells that start producing extracellular matrix (ECM) components and secrete factors that orchestrate wound healing, but also promote adverse cardiac remodeling that can progress to life-threatening heart failure (HF). Due to their vital role in the wound healing and LV remodeling after MI, (myo)fibroblasts have been receiving more and more attention lately as targets for anti-HF treatment strategies. In this review, we will summarize the current knowledge regarding the cardiac (myo)fibroblast characteristics, discuss the signaling pathways and the factors that affect their migration, proliferation and differentiation post-MI, as well as their ECM-depositing capabilities. Finally, we will provide an overview of the latest innovative research that is targeting the (myo)fibroblast, in an attempt to limit adverse remodeling and prevent HF.
心肌梗死（MI）后，会启动一个称为伤口愈合的动态复杂过程，旨在形成坚固的瘢痕并限制左心室（LV）的不良重塑。心脏成纤维细胞（CFs）是心脏中数量最多的细胞类型，在心肌梗死后的机械应力、转化生长因子β（TGF-β）和各种炎症信号的影响下分化为肌成纤维细胞。肌成纤维细胞是收缩性细胞，开始产生细胞外基质（ECM）成分并分泌协调伤口愈合的因子，但也会促进可能发展为危及生命的心力衰竭（HF）的不良心脏重塑。由于（肌）成纤维细胞在心肌梗死后的伤口愈合和左心室重塑中起着至关重要的作用，它们作为抗心力衰竭治疗策略的靶点最近受到了越来越多的关注。在这篇综述中，我们将总结关于心脏（肌）成纤维细胞特征的现有知识，讨论影响其在心肌梗死后迁移、增殖和分化的信号通路及因素，以及它们的ECM沉积能力。最后，我们将概述针对（肌）成纤维细胞的最新创新性研究，以试图限制不良重塑并预防心力衰竭。
