Dynamic and static biomechanical traits of cardiac fibrosis

Abstract

Cardiac fibrosis is a common pathology in cardiovascular diseases which are reported as the leading cause of death globally. In recent decades, accumulating evidence has shown that the biomechanical traits of fibrosis play important roles in cardiac fibrosis initiation, progression and treatment. In this review, we summarize the four main distinct biomechanical traits (i.e., stretch, fluid shear stress, ECM microarchitecture, and ECM stiffness) and categorize them into two different types (i.e., static and dynamic), mainly consulting the unique characteristic of the heart. Moreover, we also provide a comprehensive overview of the effect of different biomechanical traits on cardiac fibrosis, their transduction mechanisms, and in-vitro engineered models targeting biomechanical traits that will aid the identification and prediction of mechano-based therapeutic targets to ameliorate cardiac fibrosis.

Progress on role of ion channels of cardiac fibroblasts in fibrosis

“…ECM reconstruction is the key to cardiac reconstruction. Cardiac injury induces the hyperplasia of fibroblasts and trigger them to proliferate and differentiate into ECM-secreting MFs, which have a strong ability to produce ECM proteins and cause collagen accumulation, namely, myocardial fibrosis ( Nakagawa et al, 2008 ; Liu et al, 2022 ). MFs are fibroblasts with transformed phenotype and the characteristics of smooth muscle ( Yu et al, 2018 ).…”

Construction of cardiac fibrosis for biomedical research

“…Current research suggests that immoderate stretching could act as a significant stimulant for myocardial injury and continuing activation of myofibroblasts, ultimately leading to the development of fibrosis. [93][94][95] McCain et al imitated mechanical overexertion by circularly stretching designed layered cardiovascular tissues on an elastic chip. 96 Periodic stretching was found to activate indicators of abnormal heart hypertrophy, change myocyte morphology and filament orientation, modify calcium transient, and diminish stress production.…”

“…In addition, continuous stretch at the cellular level is caused by the regular rhythm of cardiomyocytes and, to a lesser extent, by the contraction of myofibroblasts. Current research suggests that immoderate stretching could act as a significant stimulant for myocardial injury and continuing activation of myofibroblasts, ultimately leading to the development of fibrosis 93–95 . McCain et al.…”

In Vitro Mechanical Stimulation to Reproduce the Pathological Hallmarks of Human Cardiac Fibrosis on a Beating Chip and Predict The Efficacy of Drugs and Advanced Therapies

“…[8] In this scenario, 2D in vitro cell culture models have been extensively used in the last decades to study fibrotic remodeling and the role of both biochemical and biophysical pro-fibrotic factors in the pathology. [9] Specifically, biophysical cues have been investigated by tailoring the mechanical properties of cell culture supports or through the application of an active cyclic stretching to the cultures. [8][9][10][11] Nevertheless, 2D models often failed to recapitulate the native microenvironment and the biophysical stimuli that fundamentally contribute to the pathology, leading to imperfect or even misleading results on drug effects.…”

“…[9] Specifically, biophysical cues have been investigated by tailoring the mechanical properties of cell culture supports or through the application of an active cyclic stretching to the cultures. [8][9][10][11] Nevertheless, 2D models often failed to recapitulate the native microenvironment and the biophysical stimuli that fundamentally contribute to the pathology, leading to imperfect or even misleading results on drug effects. [10,11] Similarly, animal models exploited to investigate the fibrotic remodeling process mainly fail in reproducing the human responses mostly because of interspecies differences.…”