BETs that cover the spread from acquired to heritable heart failure

Heart failure (HF) with reduced contractile function is a common and lethal syndrome in which the heart cannot pump blood to adequately meet bodily demands, resulting in high mortality despite the current standard of care. In modern societies, the most common drivers of HF are ischemic heart disease and hypertension. However, in a substantial subset of cases, patients present with dilated and poorly contracting hearts without evidence of common inciting stressors, a syndrome called dilated cardiomyopathy (DCM). Genome sequencing has identified a host of deleterious germline variants in key cardiomyocyte genes as causes of heritable DCM, including mutations in LMNA, which encodes the nuclear lamina-associated protein lamin A/C. In this issue of the JCI, Auguste et al. generate a mouse model of DCM in which they delete Lmna in cardiomyocytes and discover that bromodomain and extraterminal (BET) protein activation is a druggable epigenetic mechanism of disease pathogenesis in this heritable HF syndrome.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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In this study we aimed to evaluate management strategies in our pediatric cardiac transplantation candidates with PH and high PVR prior to OHT. METHOD: Twenty-six cardiac transplantation candidates (age: 10.2 ± 4.6, 1-17 years) underwent cardiac catheterization for the determination of PVR and pulmonary arterial pressure. They were admitted to the hospital and received 1-3 days of intravenous (IV) vasodilator therapy; 0.5-3 μg/kg/min nitroglyserin and/or 0.5-3 μg/kg/min nitroprusside, 5-15 μg/kg/min dobutamin and/or dopamin to keep systolic blood pressure above 80 mmHg. RESULTS: Thirteen patients ...
Source: The Turkish Journal of Pediatrics - Category: Pediatrics Authors: Tags: Turk J Pediatr Source Type: research
In conclusion, AF seems to have a higher prevalence in the general population than previously thought, and is mostly associa ted with hypertension, cardiomyopathy and rheumatic heart disease in SSA. It is associated with a high incidence of heart failure and stroke. The management of AF is suboptimal in SSA, especially with a low uptake of oral anticoagulation.This article is protected by copyright. All rights reserved.
Source: Journal of Cardiovascular Electrophysiology - Category: Cardiology Authors: Tags: COMPREHENSIVE REVIEWS Source Type: research
AbstractHeart diseases are a major cause of morbidity and mortality world-wide. Lysyl oxidase (LOX) and related LOX-like (LOXL) isoforms play a vital role in remodelling the extracellular matrix (ECM). The LOX family controls ECM formation by cross-linking collagen and elastin chains. LOX/LOXL proteins are copper-dependent amine oxidases that catalyse the oxidation of lysine, causing cross-linking between the lysine moieties of lysine-rich proteins. Dynamic changes in LOX and LOXL protein-expression occur in a variety of cardiac pathologies; these changes are believed to be central to the associated tissue-fibrosis. An awa...
Source: Cardiovascular Research - Category: Cardiology Source Type: research
In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study was carried out in accordance with the recommendations of “Guide for the Care and Use of Laboratory Animals, National Institutes of Health.” The protocol was approved by the “China Pharmaceutical University.” Surgical Preparation The mice were anesthetized with chloral hydrate (4% chloral hydrate, ip). The HF model was induced by CAL as previously reported (Gao et al., 2010). Successful ligation of the coronary artery was confirmed by the occurrence of ST-segment elevation in electrocardiogram. Sham operated mice were performed the same process except left CAL. After ligation, the heart...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.Kidney Blood Press Res 2018;43:1865 –1877
Source: Kidney and Blood Pressure Research - Category: Urology & Nephrology Source Type: research
In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital. It may provi de precious time for heart transplantation or myocardial remodeling, improvement, and possible discontinuation even after long periods of support.
Source: Pediatric Cardiology - Category: Cardiology Source Type: research
In conclusion, HIMF has a critical role in the development of cardiac hypertrophy, and targeting HIMF may represent a potential therapeutic strategy.
Source: Hypertension - Category: Cardiology Authors: Tags: Heart Failure, Hypertrophy Original Articles Source Type: research
ConclusionHeart failure occurs at a younger age in Indians compared to the western countries. The most common etiology is DCM followed by VHD. Since this is a retrospective analysis and has its own limitations, community based heart failure study taking a clue from the present study can be done to achieve invaluable data.
Source: Journal of Indian College of Cardiology - Category: Cardiology Source Type: research
Conclusion Heart failure occurs at a younger age in Indians compared to the western countries. The most common etiology is DCM followed by VHD. Since this is a retrospective analysis and has its own limitations, community based heart failure study taking a clue from the present study can be done to achieve invaluable data.
Source: Journal of Indian College of Cardiology - Category: Cardiology Source Type: research
More News: Biomedical Science | Cardiology | Cardiomyopathy | Dilated Cardiomyopathy | Genetics | Heart | Heart Disease | Heart Failure | Hypertension