Chute Michael, Aujla Preetinder, Jana Sayantan, Kassiri Zamaneh
Department of Physiology, Cardiovascular Research Center, University of Alberta, Edmonton, AB T6G 2S2, Canada.
J Cardiovasc Dev Dis. 2019 Sep 23;6(4):35. doi: 10.3390/jcdd6040035.
The extracellular matrix (ECM) provides structural support and a microenvironmentfor soluble extracellular molecules. ECM is comprised of numerous proteins which can be broadly classified as fibrillar (collagen types I and III) and non-fibrillar (basement membrane, proteoglycans, and glycoproteins). The basement membrane provides an interface between the cardiomyocytes and the fibrillar ECM, while proteoglycans sequester soluble growth factors and cytokines. Myocardial fibrosis was originally only linked to accumulation of fibrillar collagens, but is now recognized as the expansion of the ECM including the non-fibrillar ECM proteins. Myocardial fibrosis can be reparative to replace the lost myocardium (e.g., ischemic injury or myocardial infarction), or can be reactive resulting from pathological activity of fibroblasts (e.g., dilated or hypertrophic cardiomyopathy). Contribution of fibrillar collagens to fibrosis is well studied, but the role of the non-fibrillar ECM proteins has remained less explored. In this article, we provide an overview of the contribution of the non-fibrillar components of the extracellular space of the heart to highlight the potential significance of these molecules in fibrosis, with direct evidence for some, although not all of these molecules in their direct contribution to fibrosis.
细胞外基质（ECM）为可溶性细胞外分子提供结构支持和微环境。ECM由多种蛋白质组成，大致可分为纤维状（I型和III型胶原蛋白）和非纤维状（基底膜、蛋白聚糖和糖蛋白）。基底膜在心肌细胞和纤维状ECM之间提供了一个界面，而蛋白聚糖则隔离可溶性生长因子和细胞因子。心肌纤维化最初仅与纤维状胶原蛋白的积累有关，但现在被认为是ECM的扩张，包括非纤维状ECM蛋白。心肌纤维化可以是修复性的，以替代受损的心肌（如缺血性损伤或心肌梗死），也可以是由成纤维细胞的病理活动引起的反应性纤维化（如扩张型或肥厚型心肌病）。纤维状胶原蛋白对纤维化的作用已得到充分研究，但非纤维状ECM蛋白的作用仍较少被探索。在本文中，我们概述了心脏细胞外空间非纤维状成分的作用，以突出这些分子在纤维化中的潜在意义，尽管并非所有这些分子对纤维化的直接贡献都有直接证据。
