Epigenetic regulation of extracellular matrix mechanotransduction in cardiac fibrosis

Cardiac fibroblasts activation and cardiac fibrosis is a pathophysiological repair process that respond to various detrimental stimuli in the heart, leading to reduced ventricular diastolic compliance, impaired mechanotransduction, drastic changes in heart rhythm and pumping function, and obstruction of gas-blood exchange. To some extent, these changes are reflected in the cardiac mechanotransduction remodeling, as well as changes in the quantity, composition, and hardness of extracellular matrix, hemodynamic forces, mechanosensitive signal transduction, and epigenetic regulation related to cardiac mechanics. Cardiac fibroblasts biosynthesize and secrete extracellular matrix, and even receive signals from extracellular matrix through many different surface receptors and complexes, which are important for mechanotransduction. Besides, the mechanical properties of the microenvironment are critical for ascertaining fibrotic responses and cardiac performance. This review provides an overview of the multiscale mechanics changes in the heart and details how the mechanical molecular factors influence cardiac mechanotransduction and fibrosis development. Finally, we discuss and consider how mechanically targeted agents affect these mechanotransduction events in the heart, hoping to provide insights for the future treatment of corresponding human pressure overload-induced cardiac fibrosis.