Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics

Abstract

Extracellular matrix (ECM) plays a critical role in maintaining elasticity in cardiac tissues. Elasticity is required in the heart for properly pumping blood to the whole body. Dysregulated ECM remodeling causes fibrosis in the cardiac tissues. Cardiac fibrosis leads to stiffness in the heart tissues, resulting in heart failure. During cardiac fibrosis, ECM proteins get excessively deposited in the cardiac tissues. In the ECM, cardiac fibroblast proliferates into myofibroblast upon various kinds of stimulations. Fibroblast activation (myofibroblast) contributes majorly toward cardiac fibrosis. Other than cardiac fibroblasts, cardiomyocytes, epithelial/endothelial cells, and immune system cells can also contribute to cardiac fibrosis. Alteration in the expression of the ECM core and ECM-modifier proteins causes different types of cardiac fibrosis. These different components of ECM culminated into different pathways inducing transdifferentiation of cardiac fibroblast into myofibroblast. In this review, we summarize the role of different ECM components during cardiac fibrosis progression leading to heart failure. Furthermore, we highlight the importance of applying mass-spectrometry-based proteomics to understand the key changes occurring in the ECM during fibrotic progression. Next-gen proteomics studies will broaden the potential to identify key targets to combat cardiac fibrosis in order to achieve precise medicine-development in the future.