Extracellular Matrix in Cardiac Tissue Mechanics and Physiology: Role of Collagen Accumulation

Abstract

The extracellular matrix (ECM) forms a mesh surrounding tissue, made up of fibrous and non-fibrous proteins that contribute to the cellular function, mechanical properties of the tissue and physiological function of the organ. The cardiac ECM remodels in response to mechanical alterations (e.g., pressure overload, volume overload) or injuries (e.g., myocardial infarction, bacterial infection), which further leads to mechanical and functional changes of the heart. Collagen, the most prevalent ECM protein in the body, contributes significantly to the mechanical behavior of myocardium during disease progression. Alterations in collagen fiber morphology and alignment, isoform, and cross-linking occur during the progression of various cardiac diseases. Acute or compensatory remodeling of cardiac ECM maintains normal cardiac function. However, chronic or decompensatory remodeling eventually results in heart failure, and the exact mechanism of transition into maladaptation remains unclear. This review aims to summarize the primary role of collagen accumulation (fibrosis) in heart failure progression, with a focus on its effects on myocardial tissue mechanical properties and cellular and organ functions.

Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications

“…This is consistent with the prior report of collagen content in human LV and RV determined from hydroxyproline assays ( Miles et al, 2020 ). Second, although type I collagen is the most abundant type of collagen in ventricles ( LeBar and Wang, 2021 ), the type III collagen content was significantly correlated with the M L in all ventricles and at low strains ( Figure 7B , p < 0.05). This indicates that the longitudinal elasticity partly stemmed from type III collagen recruitment.…”

A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study

“…A tightly controlled ECM turnover is necessary for normal protein function and relies on the balance between ECM synthesis and degradation [47]. When ECM turnover is disturbed, factors that contribute to the synthesis or degradation of ECM proteins will trigger acute or chronic tissue remodeling, changing the structure and mechanical function of the ECM [47].…”

“…Previous studies indicated that transforming growth factor-β (TGF-β) activation is associated with the development of CVD [48,49]. Under normal physiological circumstances, TGF-β contributes to a healthy vessel wall structure through the control of ECM protein synthesis and deposition [47]. A potential mechanism could be increased activation of TGF-β in the high-CV risk group, which may consequently lead to an increase in type I and III collagen deposition in the ECM and therefore lower excretion of these collagen peptides.…”

Pro-angiogenic Potential of Mesenchymal Stromal Cells Regulated by Matrix Stiffness and Anisotropy Mimicking Right Ventricles

“…Right ventricle (RV) failure is common in the advanced stages of pulmonary hypertension and is a useful predictor of mortality in these patients . In the process of chronic pressure overload, the failing RV becomes stiffer, more anisotropic, , and undergoes global capillary rarefaction, leading to myocardial inefficiency. − Unlike hypertensive remodeling in the left ventricle (LV), capillary rarefaction plays a critical role in hypertensive RV maladaptation, , and thus pro-angiogenic strategies could potentially offer a RV-specific therapy.…”