Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload

Abstract

Sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) and sarcolemmal Na + /Ca 2+ exchanger (NCX1) structures are involved in heart cell Ca 2+ homeostasis. Previous studies have shown discrepancies in their function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca 2+ -handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca 2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca 2+ -handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca 2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.

Myocardial proteome changes in aortic stenosis rats subjected to long‐term aerobic exercise

“…AS was surgically induced as previously described (Mazeto et al, 2021; Sant'Ana et al, 2018; Silva et al, 2022). Briefly, rats were anesthetized with a mixture of ketamine hydrochloride (50 mg/kg; i.p.)…”

“…The heart, in response to several stimuli, undergoes cardiac remodeling, defined as alterations in genome expression, which results in molecular, cellular, and interstitial changes, and clinically manifests as changes in heart size, shape, and function (Cohn et al, 2000). The rodent aortic stenosis (AS) model has been extensively used to induce cardiac remodeling, characterized by left ventricular (LV) hypertrophy, diastolic and systolic dysfunction, and HF (Mazeto et al, 2021; Sant'Ana et al, 2018, 2023; Silva et al, 2022). The mechanisms related to functional impairment in the AS heart are complex and not fully elucidated; alterations in cardiomyocytes, myocardium, and cardiac chambers are involved (Hartupee & Mann, 2017).…”

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

“…Supravalvular aortic stenosis (AoS) in young rats has been used as an experimental model to study chronic HF, initially with preserved ejection fraction which may progress to cardiac systolic insufficiency [ 23 , 58 , 59 , 60 ]. Ventricular dysfunction occurs gradually, mimicking the development of heart disease in humans.…”

Mechanical stress concealed force enhancement and ionic transient membrane potential and metabolism in akinesia of stress cardiomyopathy

“…In a mouse experimental model, Ca 2+ transient magnitude and release kinetics were largely maintained. However, impairments in diastolic Ca 2+ include reduced sarco/endoplasmic reticulum Ca 2+ -ATPase activity [127] .…”