Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease.
Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease.
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DOI：
10.1186/1755-1536-5-15
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发表时间：
2012-09-03
期刊：
影响因子：
--
通讯作者：
Kassiri Z
中科院分区：
文献类型：
--
作者：
Fan D;Takawale A;Lee J;Kassiri Z
成纤维细胞是心肌中最大的细胞群。在心脏病中，成纤维细胞的数量增加，要么是由于常驻心肌成纤维细胞的复制、循环骨髓细胞的迁移和转化，要么是由于内皮/上皮细胞转化为成纤维细胞和肌成纤维细胞。成纤维细胞的主要功能是产生构成细胞外基质（ECM）的结构蛋白。这可以是一个建设性的过程；然而，心肌成纤维细胞的过度活跃可导致心肌中ECM蛋白的过量产生和沉积，即纤维化，对心脏结构和功能产生不利影响。除了作为ECM蛋白的主要来源外，成纤维细胞还产生许多细胞因子、肽和酶，其中基质金属蛋白酶（MMPs）及其抑制剂组织金属蛋白酶抑制剂（TIMPs）直接影响ECM的周转和稳态。成纤维细胞的功能也可依次受到MMPs和TIMPs的调节。在这篇综述文章中，我们将重点关注心脏成纤维细胞在心脏ECM形成、稳态和重塑中的功能。我们将讨论心脏成纤维细胞在不同类型心脏病患者和动物模型中心肌重构中的起源和多重作用。我们将进一步概述我们从实验动物模型和改变ECM调节蛋白、MMPs和TIMPs表达的转基因小鼠中学到的知识。
Fibroblasts comprise the largest cell population in the myocardium. In heart disease, the number of fibroblasts is increased either by replication of the resident myocardial fibroblasts, migration and transformation of circulating bone marrow cells, or by transformation of endothelial/epithelial cells into fibroblasts and myofibroblasts. The primary function of fibroblasts is to produce structural proteins that comprise the extracellular matrix (ECM). This can be a constructive process; however, hyperactivity of cardiac fibroblasts can result in excess production and deposition of ECM proteins in the myocardium, known as fibrosis, with adverse effects on cardiac structure and function. In addition to being the primary source of ECM proteins, fibroblasts produce a number of cytokines, peptides, and enzymes among which matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), directly impact the ECM turnover and homeostasis. Function of fibroblasts can also in turn be regulated by MMPs and TIMPs. In this review article, we will focus on the function of cardiac fibroblasts in the context of ECM formation, homeostasis and remodeling in the heart. We will discuss the origins and multiple roles of cardiac fibroblasts in myocardial remodeling in different types of heart disease in patients and in animal models. We will further provide an overview of what we have learned from experimental animal models and genetically modified mice with altered expression of ECM regulatory proteins, MMPs and TIMPs.