Alterations in calcium regulatory protein expression in patients with preserved left ventricle systolic function and mitral valve stenosis.

ABSTRACT

BACKGROUND: In heart failure, alterations in the expression of proteins relevant to calcium homeostasis are involved in depressed contractility and diminished relaxation. However the regulation of genes expression is only partially known. The aim was to assess expression of calcium regulatory proteins in left ventricle (LV) myocardium characterised by a preserved global function in mitral valve stenosis (MVS) model but increased neurohumoral/cytokine (N/C) activation. METHODS AND RESULTS: Plasma N/C activation was evaluated in MVS-patients (n = 27), where expression of calcium regulatory proteins (L-type channel, sarcoplasmic reticulum Ca2+-ATPase type2 - SERCA2, Na+/Ca2+ exchanger -NCX, calsequestrin, phospholamban) in LV myocardium was assessed (Western Blot) in comparison with non-failing hearts (NFH). Out of all proteins assessed in MVS, only SERCA2 and NCX expression revealed highly variable changes between subjects, with significant reduction of SERCA2 (15%) level compared to NFH. Moreover, SERCA2 was negatively correlated with BNP (univariate/regression analysis r = -0.63, P = 0.005/r2 = 0.74, P <0.001, respectively), whereas NCX was positively correlated only with noradrenaline (univariate/stepwise analysis r = 0.59 P = 0.002/r2 = 0.59; P = 0.003). CONCLUSIONS: In MVS-patients LV becomes remodelled, although its global function is preserved. It seems that apart from alterations in LV load and wall stress, also such neurohumoral factors as BNP/noradrenaline may influence the Ca2+ handling proteins expression.