Involvement of L‐type calcium channel and serca2a in myocardial dysfunction induced by obesity

Abstract

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.

Estresse crônico melhora a função miocárdica sem alterar a atividade do canal-L para Ca+2 em ratos

“…The adrenal gland hypertrophy observed in this investigation is in concordance with the underlying assumption that the sympathetic-adrenomedullary system could participate in the heart's enhanced response to calcium. Our group's studies also assessed the involvement of L-type Ca 2+ channel using the calcium blocker, diltiazem; the inclusion of this drug decreased supply of Ca 2+ to the tissue 17 . The result with diltiazem did not change the papillary muscle's function between groups, suggesting that the activity of L-type Ca 2+ channel was similar in both groups.…”

“…in density or role of the L-type calcium channel have been implicated in a variety of cardiovascular diseases 16,17 . Given this information, the objective was to test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca 2+ channel activity depression.…”

Basal and �-Adrenergic Cardiomyocytes Contractility Dysfunction Induced by Dietary Protein Restriction is Associated with Downregulation of SERCA2a Expression and Disturbance of Endoplasmic Reticulum Ca2+Regulation in Rats

“…This transporter is responsible for the higher rate of re-uptake of cytosolic Ca 2+ (90%) [20] and its expression, structure and/or function are often impaired in heart diseases with different aetiologies, such as diabetes mellitus, hypertension, and autoimmune cardiomyopathies [11,21]. Pathological changes of SERCA2a resulted in a lower re-uptake of cytosolic Ca 2+ into the sarcoplasmic reticulum, and an increased cytosolic Ca 2+ concentration, impairing cell relaxation [22,23]. Thus, it is not unrealistic to assume that the lower activity of SERCA2a induced by low protein applied in the experimental model investigated may be related to attenuation of cardiomyocyte relaxation.…”

Cardiac Ion Channel Regulation in Obesity and the Metabolic Syndrome: Relevance to Long QT Syndrome and Atrial Fibrillation

“…For example, in rats fed a high-fat diet for 15 weeks, obesity reduced Ca influx, while gene expression of CACNAC1 was either decreased (Leopoldo et al, 2011) or unchanged (Lima-Leopoldo et al, 2008). However, in another study Leopoldo et al found that mRNA expression of L-type Ca channel is increased at 30 weeks (Lima-Leopoldo et al, 2013).…”