Book ChapterDOI
What causes a broken heart--molecular insights into heart failure.
Sean P. Barry,Paul A. Townsend +1 more
TLDR
The molecular changes which occur in the heart in response to increased load and the pathways which control cardiac hypertrophy, calcium homeostasis, and immune activation during HF are reviewed and the newly emerging roles of microRNAs in regulating left ventricular dysfunction and fibrosis are discussed.Abstract:
Our understanding of the molecular processes which regulate cardiac function has grown immeasurably in recent years. Even with the advent of β-blockers, angiotensin inhibitors and calcium modulating agents, heart failure (HF) still remains a seriously debilitating and life-threatening condition. Here, we review the molecular changes which occur in the heart in response to increased load and the pathways which control cardiac hypertrophy, calcium homeostasis, and immune activation during HF. These can occur as a result of genetic mutation in the case of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) or as a result of ischemic or hypertensive heart disease. In the majority of cases, calcineurin and CaMK respond to dysregulated calcium signaling and adrenergic drive is increased, each of which has a role to play in controlling blood pressure, heart rate, and left ventricular function. Many major pathways for pathological remodeling converge on a set of transcriptional regulators such as myocyte enhancer factor 2 (MEF2), nuclear factors of activated T cells (NFAT), and GATA4 and these are opposed by the action of the natriuretic peptides ANP and BNP. Epigenetic modification has emerged in recent years as a major influence cardiac physiology and histone acetyl transferases (HATs) and histone deacetylases (HDACs) are now known to both induce and antagonize hypertrophic growth. The newly emerging roles of microRNAs in regulating left ventricular dysfunction and fibrosis also has great potential for novel therapeutic intervention. Finally, we discuss the role of the immune system in mediating left ventricular dysfunction and fibrosis and ways this can be targeted in the setting of viral myocarditis.read more
Citations
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Journal ArticleDOI
Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy
Claudia Bang,Sandor Batkai,Seema Dangwal,Shashi Kumar Gupta,Ariana Foinquinos,Angelika Holzmann,Annette Just,Janet Remke,Karina Zimmer,Andre Zeug,Evgeni Ponimaskin,Andreas Schmiedl,Xiaoke Yin,Manuel Mayr,Rashi Halder,Andre Fischer,Stefan Engelhardt,Yuanyuan Wei,Andreas Schober,Jan Fiedler,Thomas Thum +20 more
TL;DR: It is found that cardiac fibroblasts secrete star miRNA-enriched exosomes and fibroblast-derived miR-21* is identified as a paracrine signaling mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target.
Journal ArticleDOI
The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Ahmet Ucar,Shashi Kumar Gupta,Jan Fiedler,Erdem Erikci,Michal Kardasinski,Sandor Batkai,Seema Dangwal,Regalla Kumarswamy,Claudia Bang,Angelika Holzmann,Janet Remke,Massimiliano Caprio,Claudia Jentzsch,Stefan Engelhardt,Sabine Geisendorf,Carolina Glas,Thomas G. Hofmann,Michelle Nessling,Karsten Richter,Mario Schiffer,Mario Schiffer,Lucie Carrier,L. Christian Napp,Johann Bauersachs,Kamal Chowdhury,Thomas Thum +25 more
TL;DR: Pharmacological inhibition of miR-132 by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure.
Journal ArticleDOI
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin
Baoxu Pang,Xiaohang Qiao,Lennert Janssen,Arno Velds,Tom A.M. Groothuis,Ron M. Kerkhoven,Marja Nieuwland,Huib Ovaa,Sven Rottenberg,Olaf van Tellingen,Jeroen Janssen,Peter C. Huijgens,Wilbert Zwart,Jacques Neefjes +13 more
TL;DR: It is shown that anthracyclines promote histone eviction irrespective of their ability to induce DNA double-strand breaks, which has important consequences for DNA damage responses, epigenetics, transcription, side effects and cancer therapy.
Journal ArticleDOI
Curcumin, the golden spice in treating cardiovascular diseases.
Hong Li,Antoni Sureda,Hari Prasad Devkota,Valeria Pittalà,Davide Barreca,Ana Sanches Silva,Devesh Tewari,Suowen Xu,Seyed Mohammad Nabavi +8 more
TL;DR: This review systematically analyze the preclinical studies of curcumin in CVDs such as cardiac hypertrophy, heart failure, drug-induced cardiotoxicity, myocardial infarction, atherosclerosis, abdominal aortic aneurysm, stroke and diabetic cardiovascular complications.
Journal ArticleDOI
Phytochemical Antioxidants Modulate Mammalian Cellular Epigenome: Implications in Health and Disease
Smitha Malireddy,Sainath R. Kotha,Jordan D. Secor,Travis O. Gurney,Jamie L. Abbott,Gautam Maulik,Krishna Rao Maddipati,Narasimham L. Parinandi +7 more
TL;DR: The mechanisms of modulation of the mammalian cellular epigenome by the phytochemical phenolic antioxidants with implications in human diseases are discussed.
References
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Journal ArticleDOI
Prognostic Implications of Echocardiographically Determined Left Ventricular Mass in the Framingham Heart Study
TL;DR: The estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors, and it is concluded that an increase in left Ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.
Journal ArticleDOI
Calcium signalling: dynamics, homeostasis and remodelling
TL;DR: The Ca2+-signalling toolkit is used to assemble signalling systems with very different spatial and temporal dynamics and has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease.
Journal ArticleDOI
Histone deacetylases (HDACs): characterization of the classical HDAC family
Annemieke J.M. de Ruijter,Albert H. van Gennip,Huib N. Caron,Stephan Kemp,André B.P. van Kuilenburg +4 more
TL;DR: In this paper, a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity is presented.
Journal ArticleDOI
Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy
Marco Sandri,Claudia Sandri,Alexander Gilbert,Carsten Skurk,Elisa Calabria,Anne Picard,Kenneth Walsh,Stefano Schiaffino,Stewart H. Lecker,Alfred L. Goldberg +9 more
TL;DR: It is shown that in cultured myotubes undergoing atrophy, the activity of the PI3K/AKT pathway decreases, leading to activation of Foxo transcription factors and atrogin-1 induction.
Journal ArticleDOI
A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy
Jeffery D. Molkentin,Jeffery D. Molkentin,Jianrong Lu,Christopher L. Antos,Bruce E. Markham,James A. Richardson,Jeffrey Robbins,Stephen R. Grant,Eric N. Olson +8 more
TL;DR: It is shown that cardiac hypertrophy is induced by the calcium-dependent phosphatase calcineurin, which dephosphorylates the transcription factor NF-AT3, enabling it to translocate to the nucleus.