Importance of SERCA2a on early isolated diastolic dysfunction induced by supravalvular aortic stenosis in rats

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.

Cardio-omentopexy Reduces Cardiac Fibrosis and Heart Failure After Experimental Pressure Overload

“…In our study, the period of aortic banding was 16 weeks, and we found the similar result of SERCA2a expression. Silveira and colleagues [12] also observed that quantified SERCA2a was similar between sham and aortic banding. One could speculate that SERCA2a expression is maintained in compensated hypertrophy, characterized by mild abnormalities of systolic function as seen in this study.…”

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

“…Few studies have investigated Ca 2+ -transient proteins in experimental models of heart aggression with the above features, even though they should be considered part of the mechanisms involved in cardiac function loss. Some results in this area found that SERCA2a (9,10) is reduced in AoS (11,(17)(18)(19). Also, a study using rats 6 weeks after AoS found that SERCA2a is related to functional changes (11).…”

“…There are several experimental models for studying CR, one being the pressure overload model (4)(5)(6)(7)(8)(9)(10)(11)(12). Pulmonary artery stenosis (7,8), abdominal aortic stenosis (9,10), and supravalvar aortic stenosis (AoS) (1,3,5,6) are examples of interventions used to study this condition.…”

“…Pulmonary artery stenosis (7,8), abdominal aortic stenosis (9,10), and supravalvar aortic stenosis (AoS) (1,3,5,6) are examples of interventions used to study this condition. AoS has been used to promote the gradual development of left ventricular hypertrophy in young rats (1,3,5,6), with the effects appearing as weeks go by (3,5,11,12).…”

“…Some results in this area found that SERCA2a (9,10) is reduced in AoS (11,(17)(18)(19). Also, a study using rats 6 weeks after AoS found that SERCA2a is related to functional changes (11). NCX1 was enhanced in hypertrophied hearts after infarction (20) but was at normal levels shortly after pressure overload (21).…”