Myocardial fibrosis in congenital and pediatric heart disease

Abstract

Cardiac fibrosis is a common phenomenon in different types of heart diseases, such as ischemic heart disease, inherited cardiomyopathy mutations, diabetes, and ageing and is associated with morbidity and mortality. Increased accumulation of extracellular matrix (ECM) that impacts cardiac function, is the underlying cause of fibrotic heart disease. There are four different types of cardiac fibrosis, including, reactive interstitial fibrosis, replacement fibrosis, infiltrative interstitial fibrosis and endomyocardial fibrosis. They are involved in the activation and transformation of cardiac fibroblasts to myofibroblasts, which participate in ECM production and fibrotic process and several inflammatory pathways. Besides the ECM proteins, myofibroblasts also express smooth muscle α-actin, SM22 and caldesmon and other markers related to fibrotic process. Most commonly employed techniques to assess myocardial fibrosis include stress echocardiography, cardiac magnetic resonance imaging and positron emission tomography. Because of the involvement of renin-angiotensin-II-aldosterone system, transforming growth factor-β signaling and activin-linked kinase 5 in the mechanisms of cardiac fibrosis, these pathways and the involved proteins are useful as therapeutic targets. However, because of the importance of these pathways in many other physiological functions, their therapeutic targeting needs to be approached with caution.

miR-133: A Suppressor of Cardiac Remodeling?

“…The harmful stimulus induces cardiac fibroblasts to transiently express α-smooth muscle actin (α-SMA), an actin isoform that is a marker for myfibroblast and mainly responsible for the homeostasis of the ECM (Hinz et al, 2001 ). The α-SMA protein in cardiac fibroblasts is connected to the ECM through focal adhesions, and is assembled into stress fibers and remodels the surrounding ECM in response to certain types of stress, eventually causing HF (Leask, 2015 ; Tian et al, 2017 ). Although several studies have explored the origin of cardiac fibroblasts, accurate answers are still unavailable.…”

Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

“…It is a common theme in several types of heart diseases, including inherited cardiomyopathies, ischemic heart disease, diabetes and obesity, and ageing, and has been linked to morbidity and mortality [3]. During cardiac fibrosis, cardiac fibroblasts transform to a myofibroblast phenotype [3,4]. These myofibroblasts are responsible for the production of the extracellular matrix (ECM) and activation of several inflammatory pathways [5].…”

“…As a result, the interconversion of fibroblasts to myofibroblasts is prolonged. Alterations of the myocardial architecture of the injured heart contributes to impaired cardiac function and ventricular stiffness, leading to contractile dysfunction [4]. The accumulation of the ECM can also alter the mechano-electric coupling of cardiomyocytes, thereby amplifying the risk of arrhythmogenicity.…”

“…Understanding the mechanisms responsible for the initiation and subsequent progression of cardiac fibrosis are crucial to identify effective anti-fibrotic treatment options. It has been demonstrated that cardiac injury promotes the activation of the renin-angiotensin-aldosterone system (RAAS), of which angiotensin II (Ang-II) appears to be the principal effector [4]. Ang II is heavily involved with the inflammatory response since it is activated and expressed by both macrophages as well as myofibroblasts [3].…”

Development of endomyocardial fibrosis model using a cell patterning technique: In vitro interaction of cell coculture of 3T3 fibroblasts and RL-14 cardiomyocytes

“…The platform developed in this study allowed to evaluate the cellular structure and interactions in EMF in an in vitro model using patterns with complex microarchitectures. When comparing the results obtained from this study with those reported from pathological samples of explanted EMF tissues [52], it was found that the irregular pattern characterized by a distribution of ramifications in the tissue geometry causes more tissue remodeling for the affected area and more cardiomyocyte morphological changes than the compact pattern, generating cells agglomerations [53]. In contrast, the compact pattern presented a lower index of tissue remodeling than the irregular pattern.…”