Abstract
Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group (n = 6) or subjected to abdominal aortic banding (AAB) and divided into three subgroups, depending on their diet: standard (AAB + SD, n = 8), hypecaloric (AAB + HD, n = 8) and hypecaloric with discontinuous ALA treatment (AAB + HD + ALA, n = 9). Body weight (BW), glycemia, echocardiography parameters and plasma hydroperoxides were monitored throughout the study. After 36 weeks, plasma adiposity (leptin and adiponectin) and inflammation (IL-6 and TNF-alpha) markers, together with B-type natriuretic peptide and oxidative stress markers (end-products of lipid peroxidation and endogenous antioxidant systems) were assessed. Moreover, cardiac fiber diameters were measured. In our experiment, diet-induced obesity generated cardiometabolic disturbances, and in association with pressure-overload induced by AAB, it precipitated the onset of heart failure, cardiac hypertrophy and diastolic dysfunction, while producing a pro-oxidant and pro-inflammatory plasmatic status. In relationship with its antioxidant effects, the chronic ALA-discontinuous treatment prevented BW gain and decreased metabolic and cardiac perturbations, confirming its protective effects on the cardiovascular system.
Highlights
Heart failure (HF) is a clinical syndrome associated with a significant risk of mortality, hospitalization and impairment of quality of life [1]
Half of all HF patients are currently diagnosed with HF with preserved ejection fraction (HFpEF) and it is estimated that its prevalence will soon exceed that of the other HF subtypes [2,3], especially due to population aging, the increased global incidence of obesity, as well as metabolic and cardiovascular disorders derived from excess adipose tissue [2,4]
Concerning food pellets consumption throughout the study, animals fed with hypercaloric diet (AAB + HD and abdominal aortic banding (AAB) + HD + alpha-lipoic acid (ALA) groups) consumed a significantly (p < 0.05) lower quantity of food pellets compared to those fed with standard diet (AAB + SD and Control groups) (Figure 2b)
Summary
Heart failure (HF) is a clinical syndrome associated with a significant risk of mortality, hospitalization and impairment of quality of life [1]. HFpEF is mainly characterized by signs and symptoms typical for HF (dyspnea, fatigue, intolerance to effort, peripheral edema, etc.), normal or mildly reduced ejection fraction (EF ≥ 50%), left ventricular (LV) hypertrophy, left atrial enlargement and/or diastolic dysfunction [1,5,6]. HFpEF is a multifactorial disease; most patients are elderly and most often women, with a history of hypertension, obesity, diabetes mellitus, hyperlipidemia, atrial fibrillation or renal dysfunctions, while heart failure with reduced ejection fraction (HFrEF) develops more frequently in men with a history of myocardial ischemic events and myocardial infarction [1,5,6,7,8]. Studies suggest that the main link between comorbidities and HFpEF seems to be a systemic pro-inflammatory state [12,13,14] with multiple triggers that subsequently affects coronary microvascular endothelium function, cardiomyocyte structure and heart function [12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
