Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases

Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases - PubMed

Review

Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases

Yonggang Wang et al. Oxid Med Cell Longev. 2014.

Abstract

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors which contribute to CVD is required in order to develop more effective treatment options. Dysregulation of epigenetic posttranscriptional modifications of histones in chromatin is thought to be associated with the pathology of many disease models, including CVD. Histone acetyltransferases (HATs) and deacetylases (HDACs) are regulators of histone lysine acetylation. Recent studies have implicated a fundamental role of reversible protein acetylation in the regulation of CVDs such as hypertension, pulmonary hypertension, diabetic cardiomyopathy, coronary artery disease, arrhythmia, and heart failure. This reversible acetylation is governed by enzymes that HATs add or HDACs remove acetyl groups respectively. New evidence has revealed that histone acetylation regulators blunt cardiovascular and related disease states in certain cellular processes including myocyte hypertrophy, apoptosis, fibrosis, oxidative stress, and inflammation. The accumulating evidence of the detrimental role of histone acetylation in cardiac disease combined with the cardioprotective role of histone acetylation regulators suggests that the use of histone acetylation regulators may serve as a novel approach to treating the millions of patients afflicted by cardiac diseases worldwide.

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Figures

**Figure 1**
HATs classifications. HATs are categorized into two types: type A and type B; type A are nuclear HATs; type B are cytoplasmic HATs. Type A HATs are further divided into five families: GNAT family, p300/CBP family, MYST family, basal TF family, and NRCF family. Type B HATs are further divided into HAT1, HAT2, HatB3.1, Rtt109, and HAT4.

**Figure 2**
HDACs classifications. HDACs have two subclasses: zinc-dependent and NAD(+)-dependent, which are further divided into four major classes: class I HDACs (HDAC1, 2, 3, and 8); class II HDACs are divided into IIa (HDAC4, 5, 7, and 9) and IIb (HDAC6 and 10); class III HDACs (SIRT1-7); and class IV (HDAC11).

**Figure 3**
The protective effect of HDAC inhibitors in cardiac remodeling. Many risk factors such as high glucose (HG), myocardial infarction (MI), hypertension (HP), hyperlipidaemia (HLP), genetic causes (cardiomyopathy), obesity, and aging cause cardiac injury, activate pathological cellular processes (inflammation, apoptosis, oxidative stress, and fibrosis), and induce cardiac hypertrophy, remodeling, and dysfunction. HDAC inhibitors are capable of blocking elements of these detrimental biological processes and preserving cardiac function. The HDAC inhibitors, trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), scriptaid, and apicidin-derivative (Api-D) have been tested in rodent heart failure models.

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