Publication Date

2013

Journal

The Texas Heart Journal

PMID

23914011

Publication Date(s)

2013

Language

English

PMCID

PMC3709230

PubMedCentral® Posted Date

2013

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Acid Anhydride Hydrolases, Animals, Aorta, Biomarkers, Calcium, Calcium-Binding Proteins, Disease Models, Animal, Hemodynamics, Homeostasis, Hypertrophy, Left Ventricular, Myocardial Contraction, Myocardium, Phosphorylation, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Sus scrofa, Time Factors, Ventricular Dysfunction, Left, Ventricular Function, Left, Acylphosphatase

Abstract

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a peak at 6 hr and a return to baseline at 168 hr. At each observational time, SERCA2a activity, Ca2+ uptake, and acylphosphatase activity rose significantly, with a maximum increase at 6 hr. These changes indicated a higher expression of these proteins; conversely, phospholamban did not show significant changes in its concentration or in its phosphorylation status. Nuclear proto-oncogene c-fos expression rose at 6 hr. A strong inverse correlation was found when Ca2+-ATPase activity, Ca2+-ATPase expression, Ca2+ uptake, and acylphosphatase were compared with indices of systolic function. In our model of induced pressure overload, an initial phase of depressed myocardial contractility was accompanied by an increased sarcoplasmic reticulum function and by higher Ca2+-ATPase and Ca2+ uptake activities mediated by acylphosphatase. This new finding of Ca2+ homeostasis might indicate a compensatory mechanism for mechanical stress. Further studies are needed to confirm our findings.

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