Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia.
Mol Cell Biochem. 2022 May;477(5):1621-1628. doi: 10.1007/s11010-022-04399-z. Epub 2022 Feb 27.
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 Ca-handling proteins, Ca-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 Ca concentrations. We further discovered that HHcy is not associated with increased oxidative stress in SR. Taken together, these findings suggest that disturbances in SR Ca handling, caused by altered protein contents but not oxidative damage, may contribute to impaired cardiac contractility in HHcy.
血浆同型半胱氨酸（Hcy）浓度升高是心血管疾病的独立危险因素，但高同型半胱氨酸血症（HHcy）导致心脏功能障碍的机制在很大程度上尚不清楚。本研究旨在探讨肌浆网在 HHcy 引起的心脏收缩功能障碍中的作用。通过每天两次皮下注射 Hcy（0.45 μmol/g 体重），持续 2 周，诱导 HHcy，导致左心室压力和心室舒张最大速率显著降低。我们的结果表明，肌浆网 Ca 处理蛋白、Ca-ATP 酶（SERCA2）、钙调蛋白和富含组氨酸的钙结合蛋白的含量显著减少，而磷蛋白的含量不变。此外，我们发现 PLN：SERCA2 比值的增加导致在低游离 Ca 浓度时 SERCA2 活性受到抑制。我们进一步发现，HHcy 与肌浆网中氧化应激的增加无关。综上所述，这些发现表明，SR Ca 处理的紊乱可能是由蛋白含量的改变而不是氧化损伤引起的，可能导致 HHcy 中心脏收缩力受损。
