87 research outputs found
Desmin mediates TNF-뱉induced aggregate formation and intercalated disk reorganization in heart failure
We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor α (TNF-α)âinduced cardiomyopathy. We demonstrate that in mice overexpressing TNF-α in the heart (αâmyosin heavy chain promoter-driven secretable TNF-α [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and ÎČ-catenin show similar localization changes in a desmin-dependent fashion. To address underlying mechanisms, we examined whether desmin is a substrate for caspase-6 in vivo as well as the implications of desmin cleavage in MHCsTNF mice. We generated transgenic mice with cardiac-restricted expression of a desmin mutant (D263E) and proved that it is resistant to caspase cleavage in the MHCsTNF myocardium. The aggregates are diminished in these mice, and D263E desmin, desmoplakin, and ÎČ-catenin largely retain their proper ID localization. Importantly, D263E desmin expression attenuated cardiomyocyte apoptosis, prevented left ventricular wall thinning, and improved the function of MHCsTNF hearts
Cardiovascular risk in high-hazard occupations: the role of occupational cardiology
Abstract
Work is beneficial for health, but many individuals develop cardiovascular disease (CVD) during their working lives. Occupational cardiology is an emerging field that combines traditional cardiology sub-specialisms with prevention and risk management unique to specific employment characteristics and conditions. In some occupational settings incapacitation through CVD has the potential to be catastrophic due to the nature of work and/or the working environment. These are often termed 'hazardous' or 'high-hazard' occupations. Consequently, many organizations that employ individuals in high-hazard roles undertake pre-employment medicals and periodic medical examinations to screen for CVD. The identification of CVD that exceeds predefined employer (or regulatory body) risk thresholds can result in occupational restriction, or disqualification, which may be temporary or permanent. This article will review the evidence related to occupational cardiology for several high-hazard occupations related to aviation and space, diving, high altitude, emergency workers, commercial transportation, and the military. The article will focus on environmental risk, screening, surveillance, and risk management for the prevention of events precipitated by CVD. Occupational cardiology is a challenging field that requires a broad understanding of general cardiology, environmental, and occupational medicine principles. There is a current lack of consensus and contemporary evidence which requires further research. Provision of evidence-based, but individualized, risk stratification and treatment plans is required from specialists that understand the complex interaction between work and the cardiovascular system. There is a current lack of consensus and contemporary evidence in occupational cardiology and further research is required
CTH/MPST double ablation results in enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS/sGC pathway
The prognostic effect of cardiac rehabilitation in the era of acute revascularisation and statin therapy : A systematic review and meta-analysis of randomized and non-randomized studies - The Cardiac Rehabilitation Outcome Study (CROS)
BACKGROUND: The prognostic effect of multi-component cardiac rehabilitation (CR) in the modern era of statins and acute revascularisation remains controversial. Focusing on actual clinical practice, the aim was to evaluate the effect of CR on total mortality and other clinical endpoints after an acute coronary event. DESIGN: Structured review and meta-analysis. METHODS: Randomised controlled trials (RCTs), retrospective controlled cohort studies (rCCSs) and prospective controlled cohort studies (pCCSs) evaluating patients after acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) or mixed populations with coronary artery disease (CAD) were included, provided the index event was in 1995 or later. RESULTS: Out of nâ=â18,534 abstracts, 25 studies were identified for final evaluation (RCT: nâ=â1; pCCS: nâ=â7; rCCS: nâ=â17), including nâ=â219,702 patients (after ACS: nâ=â46,338; after CABG: nâ=â14,583; mixed populations: nâ=â158,781; mean follow-up: 40 months). Heterogeneity in design, biometrical assessment of results and potential confounders was evident. CCSs evaluating ACS patients showed a significantly reduced mortality for CR participants (pCCS: hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.20-0.69; rCCS: HR 0.64, 95% CI 0.49-0.84; odds ratio 0.20, 95% CI 0.08-0.48), but the single RCT fulfilling Cardiac Rehabilitation Outcome Study (CROS) inclusion criteria showed neutral results. CR participation was also associated with reduced mortality after CABG (rCCS: HR 0.62, 95% CI 0.54-0.70) and in mixed CAD populations. CONCLUSIONS: CR participation after ACS and CABG is associated with reduced mortality even in the modern era of CAD treatment. However, the heterogeneity of study designs and CR programmes highlights the need for defining internationally accepted standards in CR delivery and scientific evaluation
Frailty and cardiac rehabilitation : A call to action from the EAPC Cardiac Rehabilitation Section
Frailty is a geriatric syndrome characterised by a vulnerability status associated with declining function of multiple physiological systems and loss of physiological reserves. Two main models of frailty have been advanced: the phenotypic model (primary frailty) or deficits accumulation model (secondary frailty), and different instruments have been proposed and validated to measure frailty. However measured, frailty correlates to medical outcomes in the elderly, and has been shown to have prognostic value for patients in different clinical settings, such as in patients with coronary artery disease, after cardiac surgery or transvalvular aortic valve replacement, in patients with chronic heart failure or after left ventricular assist device implantation.The prevalence, clinical and prognostic relevance of frailty in a cardiac rehabilitation setting has not yet been well characterised, despite the increasing frequency of elderly patients in cardiac rehabilitation, where frailty is likely to influence the onset, type and intensity of the exercise training programme and the design of tailored rehabilitative interventions for these patients.Therefore, we need to start looking for frailty in elderly patients entering cardiac rehabilitation programmes and become more familiar with some of the tools to recognise and evaluate the severity of this condition. Furthermore, we need to better understand whether exercise-based cardiac rehabilitation may change the course and the prognosis of frailty in cardiovascular patients
Desmin is essential for the structure and function of the sinoatrial node:implications for increased arrhythmogenesis
Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex (SANcl) and its implication in arrhythmogenesis. Analysis of mice and humans (SANcl) indicated that the sinoatrial node exhibits high amounts of desmin, desmoplakin, N-cadherin, and ÎČ-catenin in structures we call âlateral intercalated disksâ connecting myocytes side by side. Examination of the SANcl from an arrhythmogenic cardiomyopathy model, desmin-deficient (Des-/-) mouse, by immunofluorescence, ultrastructural, and Western blot analysis showed that the number of these lateral intercalated disks was diminished. Also, electrophysiological recordings of the isolated compact sinoatrial node revealed increased pacemaker systolic potential and higher diastolic depolarization rate compared with wild-type mice. Prolonged interatrial conduction expressed as a longer P wave duration was also observed in Des-/mice. Upregulation of mRNA levels of both T-type Ca2+ current channels, Cav3.1 and Cav3.2, in the Des-/- myocardium (1.8- and 2.3-fold, respectively) and a 1.9-fold reduction of funny hyperpolarization-activated cyclic nucleotide-gated K+ channel 1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of Des-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared with wild-type mice. Heart rate variability analysis indicated a sympathetic predominance in Des-/- mice, which may further contribute to arrhythmogenicity. In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the SANcl. These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis
Cardiovascular phenotype of mice lacking 3-mercaptopyruvate sulfurtransferase
Rationale: Hydrogen sulfide (H2S) is a physiological mediator that regulates cardiovascular homeostasis. Three major enzymes contribute to the generation of endogenously produced H2S, namely cystathionine Îł-lyase (CSE), cystathionine ÎČ-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Although the biological roles of CSE and CBS have been extensively investigated in the cardiovascular system, very little is known about that of 3-MST. In the present study we determined the importance of 3-MST in the heart and blood vessels, using a genetic model with a global 3-MST deletion. Results: 3-MST is the most abundant transcript in the mouse heart, compared to CSE and CBS. 3-MST was mainly localized in smooth muscle cells and cardiomyocytes, where it was present in both the mitochondria and the cytosol. Levels of serum and cardiac H2S species were not altered in adult young (2â3 months old) 3-MSTâ/â mice compared to WT animals. No significant changes in the expression of CSE and CBS were observed. Additionally, 3-MSTâ/â mice had normal left ventricular structure and function, blood pressure and vascular reactivity. Interestingly, genetic ablation of 3-MST protected mice against myocardial ischemia reperfusion injury, and abolished the protection offered by ischemic pre- and post-conditioning. 3-MSTâ/â mice showed lower expression levels of thiosulfate sulfurtransferase, lower levels of cellular antioxidants and elevated basal levels of cardiac reactive oxygen species. In parallel, 3-MSTâ/â mice showed no significant alterations in endothelial NO synthase or downstream targets. Finally, in a separate cohort of older 3-MSTâ/â mice (18 months old), a hypertensive phenotype associated with cardiac hypertrophy and NO insufficiency was observed. Conclusions: Overall, genetic ablation of 3-MST impacts on the mouse cardiovascular system in an age-dependent manner. Loss of 3-MST exerts a cardioprotective role in young adult mice, while with aging it predisposes them to hypertension and cardiac hypertrophy
Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition
Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood. In this review, we describe the acute and chronic epigenetic effects of physical activity and dietary changes. We propose exercise and nutrition as potential triggers of epigenetic signals, promoting the reshaping of transcriptional programmes with effects on CVD phenotypes. Finally, we highlight recent developments in epigenetic therapeutics with implications for primary and secondary CVD prevention
The importance of return to work: How to achieve optimal reintegration in ACS patients
The vocational reintegration of patients after an acute coronary syndrome is a crucial step towards complete convalescence from the social as well as the individual point of view. Return to work rates are determined by medical parameters such as left ventricular function, residual ischaemia and heart rhythm stability, as well as by occupational requirement profile such as blue or white collar work, night shifts and the ability to commute (which is, in part, determined by physical fitness). Psychosocial factors including depression, self-perceived health situation and pre-existing cognitive impairment determine the reintegration rate to a significant extent. Patients at risk of poor vocational outcomes should be identified in the early period of rehabilitation to avoid a reintegration failure and to prevent socioprofessional exclusion with adverse psychological and financial consequences. A comprehensive healthcare pathway of acute coronary syndrome patients is initiated by cardiac rehabilitation, which includes specific algorithms and assessment tools for risk stratification and occupational restitution. As the first in its kind, this review addresses determinants and legal aspects of reintegration of patients experiencing an acute coronary syndrome, and offers practical advice on reintegration strategies particularly for vulnerable patients. It presents different approaches and scientific findings in the European countries and serves as a recommendation for action
Secondary prevention through comprehensive cardiovascular rehabilitation : from knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology
©The European Society of Cardiology 2020. Article reuse guidelines : sagepub.com/journals-permissionsSecondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and âmodernâ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.info:eu-repo/semantics/publishedVersio
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