Adapting extracellular matrix proteomics for clinical studies on cardiac remodeling post-myocardial infarction

Abstract

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve stimulation of robust inflammation to clear necrotic myocytes and tissue debris and induction of extracellular matrix (ECM) protein synthesis to generate a scar. Proteomic strategies provide us with a means to index the ECM proteins expressed in the LV, quantify amounts, determine functions, and explore interactions. This review will focus on the efforts taken in the proteomics research field that have expanded our understanding of post-MI LV remodeling, concentrating on the strengths and limitations of different proteomic approaches to glean information that is specific to ECM turnover in the post-MI setting. We will discuss how recent advances in sample preparation and labeling protocols increase our successes at detecting components of the cardiac ECM proteome. We will summarize how proteomic approaches, focusing on the ECM compartment, have progressed over time to current gel-free methods using decellularized fractions or labeling strategies that will be useful for clinical applications. This review will provide an overview of how cardiac ECM proteomics has evolved over the last decade and will provide insight into future directions that will drive forward our understanding of cardiac ECM turnover in the post-MI LV.

Proteomic analysis of the cardiac extracellular matrix: clinical research applications

“…The cardiac extracellular matrix (ECM) provides structural and biochemical support for the cell types that comprise the myocardium, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells, fibroblasts, and immune cells [1,2]. Because ECM is by nature insoluble and present in relatively low abundance compared to more prevalent cytoplasmic and mitochondrial proteins found as cell constituents, ECM proteins are often not detected during global proteomics analyses using unbiased approaches [3].…”

“…ECM proteins support physiology of the normal myocardium and regulate the extent of fibrosis and impaired physiology that occurs during disease progression. After myocardial infarction (MI), for example, the myocardium undergoes extensive protein turnover as old ECM is replaced by an infarct scar primarily composed of collagen [2,5]. Cardiac wound healing is dependent on a balance between ECM removal and synthesis of new ECM.…”

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

“…Their expression is regulated by mechanical stress both during development and in adulthood [46]. Tenascins mediate both inlammatory and ibrotic processes to enable efective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of muscle-tendinous tissue [46,89].…”

“…Cell therapy has more safety, improved cardiac function, increased healing, vascular density and increased regional circulation [45]. However, the eiciency of delivery and retention is lower than expected, and the retention and survival of cells at sites of delivery has been limited [5,46,47].…”

Atypical form of microscopic colitis in 56-year-old patient presenting with long-lasting watery diarrhea

“…Creating a new collagen network is based on the removal and formation of collagen in the extracellular matrix (ECM). The predominance of collagen degradation can lead to aneurysm formation but its excess can be a substrate for the development of arrhythmias and heart failure [4]. As a consequence of the processes discussed above, left ventricular enlargement, a change in its shape and shrinkage deterioration often occur.…”