Alteration of myocardial sarcoplasmic reticulum Ca 2+ ‐ATPase and Na + –Ca 2+ exchanger expression in human left ventricular volume overload

Background: Reduced myocardial contractility is often attributed to altered Ca 2+ transients and expression of Ca 2+ ‐ATPase of the SR (SERCA) and Na+/Ca 2+ exchanger (NCX) genes. Aims: To assess myocardial expression of SERCA and NCX protein levels in left ventricular (LV) remodelling due to chronic severe mitral regurgitation (MR). Methods: Myocardial expression of SERCA/NCX in biopsy specimens obtained during mitral surgery was assessed in 36 MR patients with LV remodelling and plasma neurohumoral/cytokine activation and in four non‐failing hearts (NFH). Results: Myocardial protein levels of SERCA were significantly (20%) lower in the MR group than in NFH group ( p =0.016). No significant changes in NCX were observed. However, a lack of homogeneity with regard to SERCA/NCX proteins was observed. Moreover, SERCA was negatively correlated with BNP ( r =–0.49, p =0.02), TNFα ( r =0.68, p =0.0005) and IL‐6 ( r =–0.52, p =0.02), whereas NCX was only negatively correlated with TNFα ( r =–0.62, p =0.002). Conclusions: MR patients showed wide variations in SERCA/NCX protein expression. Myocardial protein levels of SERCA were significantly lower in the MR population. Moreover, a correlation between BNP, cytokines (IL‐6, TNFα) and the expression of SERCA/NCX proteins was observed.