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Time course of changes in the expression of DHPR, RyR2, and SERCA2 after myocardial infarction in the rat left ventricle

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Abstract

Postinfarction left ventricular remodeling leads to the functional decline of the left ventricle (LV). Since dihydropyridine receptor (DHPR), ryanodine receptor (RyR2), and sarco-endoplasmic reticulum (SR) Ca2+-ATPase2 (SERCA2a) play a major role in the contractility of the heart, the aim of our study was to evaluate the time course of changes in the expression of these proteins 1 day, 2 weeks and 4 weeks after myocardial infarction (MI). Myocardial infarction was produced by ligation of left anterior descending coronary artery of the rat. Transthoracic echocardiography was performed to characterize structural and functional changes after MI. To evaluate protein mRNA levels and the relative amount of proteins, real-time quantitative RT-PCR and Western blotting were used. LV ejection fraction and fractional shortening decreased significantly during the 4-week follow-up period (P < 0.001). Typical features of LV remodeling after MI were seen, with a decrease in anterior wall thickness (P < 0.001) and dilatation of the LV (P < 0.001). Expression of DHPR and RyR2 mRNAs decreased and Serca2a mRNA tended to decrease 1 day after MI (P < 0.001, P < 0.01 and P = 0.06, respectively), followed by recovery of the expression during the next 4 weeks. In the infarcted hearts the quantities of SERCA2 proteins in the LV were significantly decreased at the time of 4 weeks. In conclusion, MI was associated with transient decrease in the expression of the DHPR and RyR2 mRNAs and a reduced quantity of SERCA2 proteins in the LV. Since they have a key role in the contraction of the heart, changes in the expression of these proteins may be important regulators of LV systolic function after MI.

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Acknowledgements

We are grateful to Ms. Marja-Liisa Martimo-Halmetoja, Ms. Tuula Taskinen and Ms. Sirpa Rutanen for their technical assistance. Anna Vuolteenaho, M.A., is acknowledged for revizing the English of this article. This study was supported by the Academy of Finland (Grant Nr. 102 286), the Finnish Foundation of Cardiovascular Research and the Sigrid Juselius Foundation. Graduate School of Circumpolar Wellbeing, Health, and Adaptation is also acknowledged.

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Correspondence to Pirkko Sallinen.

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Sallinen, P., Mänttäri, S., Leskinen, H. et al. Time course of changes in the expression of DHPR, RyR2, and SERCA2 after myocardial infarction in the rat left ventricle. Mol Cell Biochem 303, 97–103 (2007). https://doi.org/10.1007/s11010-007-9460-3

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