Early cardiac dysfunction is rescued by upregulation of SERCA2a pump activity in a rat model of metabolic syndrome
Article first published online: 9 MAR 2012
© 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society
Volume 205, Issue 3, pages 381–393, July 2012
How to Cite
Miklós, Z., Kemecsei, P., Bíró, T., Marincsák, R., Tóth, B. I., Op den Buijs, J., Benis, É., Drozgyik, A. and Ivanics, T. (2012), Early cardiac dysfunction is rescued by upregulation of SERCA2a pump activity in a rat model of metabolic syndrome. Acta Physiologica, 205: 381–393. doi: 10.1111/j.1748-1716.2012.02420.x
- Issue published online: 18 MAY 2012
- Article first published online: 9 MAR 2012
- Accepted manuscript online: 31 JAN 2012 05:08AM EST
- Manuscript Accepted: 23 JAN 2012
- Manuscript Revised: 21 DEC 2011
- Manuscript Revised: 26 OCT 2011
- Manuscript Received: 5 OCT 2011
- isolated hearts;
- metabolic syndrome;
Various components of metabolic syndrome associate with cardiac intracellular calcium () mishandling, a precipitating factor in the development of heart failure. We aimed to provide a thorough description of early stage -cycling alterations in the fructose-fed rat, an experimental model of the disorder, where insulin resistance, hypertension and dyslipidaemia act cooperatively on the heart.
Rats were fed with fructose-rich chow. After 6 weeks, echocardiography was performed, which was followed by measurements of myocardial transients recorded by Indo-1 surface fluorometry in isolated perfused hearts. Sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) activity was assessed by administration of its inhibitor cyclopiazonic acid (CPA). Mathematical model analysis of transients was used to estimate kinetic properties of SR Ca2+ transporters. Protein levels of key Ca2+ handling proteins were also measured.
Echocardiography showed signs of cardiac hypertrophy, but in vivo and ex vivo haemodynamic performance of fructose-fed rat hearts were unaltered. However, a decline in Ca2+ sequestration capacity ( and decay time of transients) was observed. Model estimation showed decreased affinity for Ca2+ (higher Km) and elevated Vmax for SERCA2a. Diseased hearts were more vulnerable to CPA application. Fructose feeding caused elevation in SERCA2a and phosphorylated phospholamban (PLB) expression, while total PLB level remained unchanged.
In early stage, metabolic syndrome primarily disturbs SERCA2a function in the heart, but consequential haemodynamic dysfunction is prevented by upregulation of SERCA2a protein level and phosphorylation pathways regulating PLB. However, this compensated state is very vulnerable to a further decline in SERCA2a function.