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Effect of hyperhomocysteinemia on rat cardiac sarcoplasmic reticulum

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Abstract

Increased concentration of plasma homocysteine (Hcy) is an independent risk factor of cardiovascular disease, yet the mechanism by which hyperhomocysteinemia (HHcy) causes cardiac dysfunction is largely unknown. The aim of present study was to investigate the contribution of sarcoplasmic reticulum to impaired cardiac contractile function in HHCy. HHcy-induced by subcutaneous injection of Hcy (0.45 μmol/g of body weight) twice a day for a period of 2 weeks resulted in significant decrease in developed left ventricular pressure and maximum rate of ventricular relaxation. Our results show that abundances of SR Ca2+-handling proteins, Ca2+-ATPase (SERCA2), calsequestrin and histidine-rich calcium-binding protein are significantly reduced while the content of phospholamban is unchanged. Moreover, we found that increased PLN:SERCA2 ratio results in the inhibition of SERCA2 activity at low free Ca2+ concentrations. We further discovered that HHcy is not associated with increased oxidative stress in SR. Taken together, these findings suggest that disturbances in SR Ca2+ handling, caused by altered protein contents but not oxidative damage, may contribute to impaired cardiac contractility in HHcy.

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Funding

This study was funded by grant VEGA 1/0004/19.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia

    Zuzana Tatarkova, Maria Bencurova, Jan Lehotsky, Peter Racay, Monika Kmetova Sivonova, Dusan Dobrota & Peter Kaplan

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  1. Zuzana Tatarkova
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  2. Maria Bencurova
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  7. Peter Kaplan
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Contributions

PK, ZT and JL: designed the study. ZT, MB, PR and MKS: performed the experiments and statistical analysis. DD: critically reviewed and edited the manuscript. All the authors approved the final version.

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Correspondence to Peter Kaplan.

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This study has been approved by the Ethical Committee of the Jessenius Faculty of Medicine in Martin, Slovakia.

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Tatarkova, Z., Bencurova, M., Lehotsky, J. et al. Effect of hyperhomocysteinemia on rat cardiac sarcoplasmic reticulum. Mol Cell Biochem 477, 1621–1628 (2022). https://doi.org/10.1007/s11010-022-04399-z

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