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.

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation

“…However, there are limited therapeutic approaches to effectively reduce or reverse cardiac fibrosis. Myofibroblasts are the central cellular effector in the production of collagen, which is primarily derived from cardiac resident fibroblasts [ 32 ]. Therefore, prevention of the differentiation of fibroblasts to myofibroblasts is important in inhibiting pathological cardiac fibrosis.…”

Cardiac organoid: multiple construction approaches and potential applications

“…The cardiac ECM is a critical component that not only provides structural integrity, but also plays a key role in a variety of genetic and metabolic diseases. 35 Moreover, the ECM creates a natural 3D environment favorable for cell and tissue growth, maturation and repair, with corresponding mechanical and biochemical properties that regulate cellular functions, such as cell migration and lineage qualification. 36 Cardiac ECM scaffolds mainly contain collagen I, III and IV, glycosaminoglycan, fibronectin, laminin and a small number of growth factors.…”

Rodent Models of Dilated Cardiomyopathy and Heart Failure for Translational Investigations and Therapeutic Discovery

“…Monocytes and tissue-resident macrophages then acquire a resolution (anti-inflammatory) profile and catalyze the differentiation of myofibroblasts from quiescent fibroblasts [ 145 , 146 , 147 ]. Myofibroblasts produce the extracellular matrix components that form the basis of scar formation, although if dysregulated, myofibroblasts may also promote a negative fibrotic remodeling process [ 148 ]. The inflammatory system initiates the detrimental stimulus which sustains myocardial damage in the setting of acute myocarditis or chronic inflammatory cardiomyopathy [ 149 ].…”