Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of Epigenetic Therapy

Abstract

Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure. This self-perpetuating deposition of collagen and other matrix proteins eventually alter cellular homeostasis; impair tissue elasticity and leads to multi-organ failure, as seen during pathogenesis of cardiovascular diseases, chronic kidney diseases, cirrhosis, idiopathic pulmonary fibrosis, and scleroderma. In the last 25 years, multiple studies have investigated the molecular basis of organ fibrosis and highlighted its multi-factorial genetic, epigenetic, and environmental regulation. In this minireview, we focus on five major epigenetic regulators and discuss their central role in cardiac fibrogenesis. Additionally, we compare and contrast the epigenetic regulation of hypertension-induced reactive fibrogenesis and myocardial infarction-induced reparative or replacement cardiac fibrogenesis. As microRNAs-one of the major epigenetic regulators-circulate in plasma, we also advocate their potential diagnostic role in cardiac fibrosis. Lastly, we discuss the evolution of novel epigenetic-regulating drugs and predict their clinical role in the suppression of pathological cardiac remodeling, cardiac aging, and heart failure. J. Cell. Physiol. 232: 1941-1956, 2017. © 2016 Wiley Periodicals, Inc.

A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

“…In contrast, epigenetic dysregulation contributes to the onset and progression of numerous human diseases including organ fibrosis. 3 We previously documented that epigenetic regulator FATp300—p300 with intrinsic factor acetyltransferase activity—is essential for profibrogenic-signal-induced Type I collagen synthesis and its level is significantly elevated in fibrotic tissues. 4,5 As FATp300 levels are elevated in fibrotic tissues and hypertension induces fibrogenesis in heart and kidney, we hypothesize that pharmacological inhibition of FATp300 is an ideal approach to ameliorate hypertension-associated cardio-renal fibrosis.…”

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

“…Several studies have shown that both genetic and epigenetic factors play a critical role in the expression of cardiomyogenesis genes. [4][5][6] As a common environmental teratogen, alcohol consumption during pregnancy has been reported to cause CHD in foetuses. 7,8 Unfortunately, the underlying mechanism remains unclear.…”

Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review

“…It has been reported that miRNAs modify the focal points associated with the TGF-β pathway which in turn alters the signalling process of the pathway [207]. An example of such modification of miRNAs has been implicated in its ability to control ERK-MAPK activity in a diabetic state [208].…”