Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

Watson, Chris; Horgan, Stephen; Neary, Roisín; Glezeva, Nadezhda; Tea, Isaac; Corrigan, Niamh; McDonald, Ken; Ledwidge, Mark; Baugh, John

doi:10.1177/1074248415591698

Cited by 79 publications

(62 citation statements)

References 45 publications

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“…In vivo gene transfer of these transcription factors after MI attenuated fibrosis and cardiac dysfunction [179]. Interestingly, it was recently shown that hypertrophy and fibrosis could also be treated with the administration of epigenetic drugs, such as the DNA methylation inhibitor 5-azacytidine or the previously mentioned HDAC inhibitors [180]. …”

Section: Clinical and Translational Perspectivesmentioning

confidence: 99%

A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

Schirone

Forte

Palmerio

et al. 2017

Oxidative Medicine and Cellular Longevity

333

241

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Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here, we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling.

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Section: Clinical and Translational Perspectivesmentioning

confidence: 99%

A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

Schirone

Forte

Palmerio

et al. 2017

Oxidative Medicine and Cellular Longevity

333

241

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“…Transcriptional inhibition of NF-κB, a redox-sensitive transcription factor, could inactivate antiapoptotic proteins [73] as may epigenetic modifications of myofibroblast gene expression and survival [74]. A DNA methylation inhibitor has shown promise in the treatment of hypertension-induced hypertrophy with fibrosis [75]. …”

Section: Cardioprotective Strategiesmentioning

confidence: 99%

Myofibroblast secretome and its auto-/paracrine signaling

Bomb

Heckle

Sun

et al. 2016

Expert Review of Cardiovascular Therapy

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Summary Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-β1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring. Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-β1-Smad pathway by antibody or the use of triplex-forming oligonucleotides.

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“…Так, відмічено покращення кількох ехокардіографічних показників, пов'язаних із гіпертрофією і діастолічною дисфункцією міокарда у щурів, яким вводили 5-азаци-тидин. Ці дані набули пояснення внаслідок досліджень серцевих фібробластів шлуноч-ків серця in vitro, при яких було вивлено зменшення вмісту колагену I і III, α-актину гладеньких м'язів [50].…”

Section: можливості профілактики та лікування аг через епігенетичні вunclassified

Epigenetics of Arterial Hypertension

2017

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Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

Cited by 79 publications

References 45 publications

A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

Myofibroblast secretome and its auto-/paracrine signaling

Epigenetics of Arterial Hypertension

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