Alteration of myocardial sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ 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.


OBJECTIVE
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), TNFalpha (r=-0.68, p=0.0005) and IL-6 (r=-0.52, p=0.02), whereas NCX was only negatively correlated with TNFalpha (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, TNFalpha) and the expression of SERCA/NCX proteins was observed.
Leszek
Przemyslaw
P
Heart Failure and Transplantology Department, National Institute of Cardiology, 04-628 Warsaw, Alpejska 42 St, Poland. leszekp@ikard.pl <leszekp@ikard.pl>
Szperl
Malgorzata
M
Klisiewicz
Anna
A
Janas
Jadwiga
J
Biederman
Andrzej
A
Rywik
Tomasz
T
Piotrowski
Walerian
W
Kopacz
Mieczyslaw
M
Korewicki
Jerzy
J
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000097:blood; D010210:Papillary Muscles / Q000473:pathology / Q000503:physiopathology; D012519:Sarcoplasmic Reticulum / Q000235:genetics* / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
D016207:Cytokines; D018377:Neurotransmitter Agents; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases