Epigenetics in Reactive and Reparative Cardiac Fibrogenesis

The Promise of Epigenetic Therapy

Asish K Ghosh*, Rahul Rai, Panagiotis D Flevaris, Douglas E Vaughan

*Corresponding author for this work

Research output: Contribution to journalReview article

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1941-1956
Number of pages16
JournalJournal of Cellular Physiology
Volume232
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Epigenomics
Extracellular Matrix Proteins
Fibrosis
Heart Failure
Aging of materials
Environmental regulations
Cardiovascular Diseases
Therapeutics
Medical problems
Elasticity
Idiopathic Pulmonary Fibrosis
Collagen
Tissue
Chronic Renal Insufficiency
Plasmas
Intellectual Disability
Wound Healing
Homeostasis
Myocardial Infarction
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

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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.",
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Epigenetics in Reactive and Reparative Cardiac Fibrogenesis : The Promise of Epigenetic Therapy. / Ghosh, Asish K; Rai, Rahul; Flevaris, Panagiotis D; Vaughan, Douglas E.

In: Journal of Cellular Physiology, Vol. 232, No. 8, 01.08.2017, p. 1941-1956.

Research output: Contribution to journalReview article

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