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Published on: May 10, 2021
Alterations in calcium regulatory protein expression in patients with preserved left ventricle systolic function and
Przemyslaw Leszek1, Malgorzata Szperl, Anna Klisiewicz
1National Institute of Cardiology, Warszawa, Poland. przemyslaw.leszek@ikard.pl
Insights
In mitral valve stenosis, reduced SERCA2 expression in the left ventricle is linked to neurohumoral activation, impacting calcium handling despite preserved heart function.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Heart failure involves altered calcium homeostasis proteins, affecting contractility and relaxation.
- Gene expression regulation in heart failure is not fully understood.
- Mitral valve stenosis (MVS) models show increased neurohumoral/cytokine (N/C) activation with preserved global left ventricular (LV) function.
Purpose of the Study:
- To assess calcium regulatory protein expression in LV myocardium of MVS patients with preserved global function and elevated N/C activation.
- To investigate the relationship between N/C activation markers and calcium handling proteins in MVS.
Main Methods:
- Evaluated plasma N/C activation in 27 MVS patients.
- Assessed expression of L-type channel, SERCA2, NCX, calsequestrin, and phospholamban in LV myocardium via Western Blot.
- Compared MVS patients with non-failing hearts (NFH).
Main Results:
- SERCA2 and NCX expression varied significantly among MVS patients.
- SERCA2 expression was significantly reduced by 15% compared to NFH.
- SERCA2 negatively correlated with BNP; NCX positively correlated with noradrenaline.
Conclusions:
- MVS patients exhibit LV remodeling with preserved global function.
- Neurohumoral factors like BNP and noradrenaline may influence Ca2+ handling protein expression in MVS, beyond LV load and wall stress.
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.
Related Concept Videos
Mitral Stenosis I: Introduction
Mitral Valve Prolapse I: Introduction
Mitral Stenosis II: Clinical features and Diagnostic Tests
Mitral Regurgitation I: Introduction
Mitral Valve Prolapse II: Assessment and Management
Cardiomyopathy III: Hypertrophic Cardiomyopathy

