HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Andrzej Biederman Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leszek, P. Articles by Trouvé, P. Search for Related Content PubMed PubMed Citation Articles by Leszek, P. Articles by Trouvé, P. Related Collections Cardiac - physiology Molecular biology Valve disease

Eur J Cardiothorac Surg 2006;30:737-743
© 2006 Elsevier Science NL

Reduced myocardial expression of calcium handling protein in patients with severe chronic mitral regurgitation

Przemysaw Leszek^a,_*, Jerzy Korewicki^a, Anna Klisiewicz^a, Jadwiga Janas^a, Andrzej Biederman^a, Aldona Browarek^a, Danièle Charlemagne^b, Pascal Trouvé^b

^a Institute of Cardiology, Alpejska 42 St., 04-628 Warsaw, Poland
^b INSERM, Unite 127, Hopital Lariboisiere, 41 boulevard de la Chapelle, 75475 Paris, France

Received 23 January 2006; received in revised form 29 June 2006; accepted 4 July 2006.

^_* Corresponding author. Address: Heart Failure Department, National Institute of Cardiology, Alpejska 42 St., 04-628 Warsaw, Poland. Tel.: +48 22 34 34 483; fax: +48 22 34 34 522. (Email: leszekp{at}ikard.pl).

Objective: Left ventricle (LV) function was shown to be a principal determinant of morbidity and mortality in both uncorrected and surgically corrected mitral regurgitation (MR). However, the cellular mechanisms that develop in the LV remodeling secondary to volume overload in chronic severe MR is still not well defined. In single ventricular myocyte, a reduced contraction and slowed relaxation have been mainly attributed to defective intracellular Ca²⁺ currents. Between several Ca²⁺ handling proteins, sarcoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) expression and activity determines not only the extent and rate of relaxation, but also the rate and amplitude of contraction. The aim of the study was to determine whether modifications of SERCA2 gene expression occurs in LV wall remodeling process secondary to chronic severe MR. Methods: The LV samples were obtained from 12 patients presented LV wall remodeling (LV: diastolic/systolic diameter—70 ± 7 mm vs 46 ± 10 mm; diastolic/systolic volume—260 ± 65 ml vs 102 ± 68 ml) due to chronic, severe MR. Expressions of SERCA2 isoforms—SERCA2a and 2b mRNAs were estimated by semiquantitative RT-PCR and normalized to GAPDH. The protein levels of SERCA2 were determined by Western blot after normalization to actin. Results were compared with samples from non-failing human hearts (NFH). Results: On SERCA2 mRNA levels, important reduction on both SERCA isoforms SERCA2a (–40%) and SERCA2b (–49%) compared to NFH, together with significant correlation between isoforms (r = 0.89; p = 0.01) were observed. SERCA2 protein levels were decreased (–38%) in MR compared to NFH. Also significant correlations between SERCA2a/2b and SERCA2 protein expression (r = 0.83, p = 0.017; r = 0.68, p = 0.05, respectively) were observed. Moreover, a negative correlation between protein levels of SERCA2 (r = –0.64, p = 0.053) and left ventricular diastolic diameter was observed. Conclusions: In chronic volume overload the down-regulation of SERCA2a and 2b at the mRNA and SERCA2 protein levels exist. Moreover, protein levels of SERCA2 tend to correlate to the grade of left ventricular diastolic dilatation and suggest an important role LV remodeling.

Abbreviations: ALD = aldosterone • ANGII = angiotensin II • CI = cardiac index • EDD = left ventricle end-diastolic diameter • EDV = left ventricle end-diastolic volume • EF = ejection fraction • ESD = left ventricle end-systolic diameter • ESV = left ventricle end-systolic volume • HF = heart failure • LA = left atrium • LV = left ventricle • MR = mitral regurgitation • NCX = Na⁺/Ca²⁺ exchanger • NA = noradrenaline • NFH = non-failing hearts • NYHA = New York Heart Association functional class • PRA = plasma renin activity • PAP = pulmonary artery pressure • PWP = pulmonary wedge pressure • SERCA1, 2, 2a, 2b 3 = Ca²⁺-ATPase of the sarcoplasmic reticulum—isoforms 1, 2, 2a, 2b, 3 • SR = sarcoplasmic reticulum • SVI = stroke volume index • 2D = two-dimensional transthoracic echocardiography

Key Words: Mitral regurgitation • Left ventricle remodeling • SERCA2 expression

This article has been cited by other articles:

				R. M. Suri, H. V. Schaff, J. A. Dearani, T. M. Sundt III, R. C. Daly, C. J. Mullany, M. E. Sarano, and T. A. Orszulak Determinants of early decline in ejection fraction after surgical correction of mitral regurgitation. J. Thorac. Cardiovasc. Surg., August 1, 2008; 136(2): 442 - 447. [Abstract] [Full Text] [PDF]