Abstract
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group.
Highlights
Cardiac remodeling (CR) can be defined as changes in genetic expression, reflected in alterations in molecular, structural and functional characteristics, as a response to specific aggressions, such as ischemia, inflammation, genetic mutations and volumetric or pressure overload [1,2,3]
Sham: control group submitted to surgery without clipping, n=32; AoS: aortic stenosis group submitted to surgery with clipping, n=32; BW: body weight; LV: left ventricle; RV: right ventricle; AT: atria; WW: wet weight; DW: dry weight
Sham: control group submitted to surgery without clipping, n=32; AoS: aortic stenosis group submitted to surgery with clipping, n=32; HR: heart rate; LVDD and LVSD: left ventricle diastolic and systolic diameter; RWT: relative wall thickness; LA: left atrium diameter; aortic diameter (AO): aorta diameter; EF: ejection fraction; fractional shortening (FS): midwall fraction shortening; E/A: ratio between filling flow peak (E wave) and atrial contraction flow peak (A wave)
Summary
Cardiac remodeling (CR) can be defined as changes in genetic expression, reflected in alterations in molecular, structural and functional characteristics, as a response to specific aggressions, such as ischemia, inflammation, genetic mutations and volumetric or pressure overload [1,2,3]. A wide spectrum of studies in humans relating SERCA2a to systolic HF can be found in the literature, showing a decrease in both its transcription and translation [7,8,9,10] The possibility of this protein being connected to HF pathophysiology has inspired experimental studies involving transgenic animals. There seems to be a consensus that SERCA2a levels decrease in myocardial dysfunction with severe heart failure, which are cases with both systolic and diastolic impairment induced by aortic stenosis (AoS) [18]. Despite this evidence, there is no available study evaluating the relationship between SERCA2a levels and heart function in hypertrophy models,
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