Targeting SERCA2a as an innovative approach to the therapy of congestive heart failure

被引：10
作者：
Ferrari, P. [1 ]
Micheletti, R.
Valentini, G.
Bianchi, G.
机构：
[1] Prassis Ist Ric Sigma Tau, Milan, Italy
[2] Sigmau Tau Ind Farmaceut Riunite SpA, Res & Dev, Rome, Italy
[3] Univ Vita Salute San Raffaele, Hosp San Raffaele, Chair Nephrol, Milan, Italy
来源：
MEDICAL HYPOTHESES | 2007年 / 68卷 / 05期
关键词：
D O I：
10.1016/j.mehy.2006.08.045
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
CHF prevalence is continuously increasing worldwide and maintains one of the poorest prognoses of any major disease. Abundant evidence points to derangement of Ca2+ cycling as the primary biochemical mark of the failing myocyte. Istaroxime is a novel compound with a dual mechanism of action: inhibition of Na+, K+-ATPase and stimulation of SERCA2a. The increase in cytoplasmic Ca2+ due to Na+, K+-ATPase inhibition together with greater sarcoplasmic reticulum reloading result in both increased inotropy and lusitropy. This effect is seen in normal and failing in vitro and in vivo models. Istaroxime improvement of the contraction-relaxation cycle constitutes a novel therapeutic approach to the treatment of heart failure. (c) 2006 Elsevier Ltd. ALL rights reserved.
引用
收藏
页码：1120 / 1125
页数：6
相关论文
共 36 条
[1]   Hemodynamic effects of a new inotropic compound, PST-2744, in dogs with chronic ischemic heart failure [J].
Adamson, PB ;
Vanoli, E ;
Mattera, GG ;
Germany, R ;
Gagnol, JP ;
Carminati, P ;
Schwartz, PJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2003, 42 (02) :169-173
[2]   The pathophysiology of advanced heart failure [J].
Baig, MK ;
Mahon, N ;
McKenna, WJ ;
Caforio, ALP ;
Bonow, RO ;
Francis, GS ;
Gheorghiade, M .
AMERICAN HEART JOURNAL, 1998, 135 (06) :S216-S230
[3]   Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes [J].
Bayram, M ;
De Luca, L ;
Massie, MB ;
Gheorghiade, M .
AMERICAN JOURNAL OF CARDIOLOGY, 2005, 96 (6A) :47G-58G
[4]  
Bers D.M., 2001, Excitation-Contraction Coupling and Cardiac Contractile Force, V2th
[5]   Short-term intravenous milrinone for acute exacerbation of chronic heart failure - A randomized controlled trial [J].
Cuffe, MS ;
Califf, RM ;
Adams, KF ;
Benza, R ;
Bourge, R ;
Colucci, WS ;
Massie, BM ;
O'Connor, CM ;
Pina, I ;
Quigg, R ;
Silver, MA ;
Georghiade, M .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 287 (12) :1541-1547
[6]   Inotropic therapy for heart failure: An evidence-based approach [J].
Felker, GM ;
O'Connor, CM .
AMERICAN HEART JOURNAL, 2001, 142 (03) :393-401
[7]   Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy [J].
Freeman, K ;
Lerman, I ;
Kranias, EG ;
Bohlmeyer, T ;
Bristow, MR ;
Lefkowitz, RJ ;
Iaccarino, G ;
Koch, WJ ;
Leinwand, LA .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (08) :967-974
[8]  
GHALI J, IN PRESS AM J CARDIO
[9]   The Pilot Randomized Study of Nesiritide Versus Dobutamine in Heart Failure (PRESERVD-HF) [J].
Gheorghiade, M ;
Stough, WG ;
Adams, KF ;
Jaffe, AS ;
Hasselblad, V ;
O'Connor, CM .
AMERICAN JOURNAL OF CARDIOLOGY, 2005, 96 (6A) :18G-25G
[10]   Relationship between Na+-Ca2+-exchanger protein levels and diastolic function of failing human myocardium [J].
Hasenfuss, G ;
Schillinger, W ;
Lehnart, SE ;
Preuss, M ;
Pieske, B ;
Maier, LS ;
Prestle, J ;
Minami, K ;
Just, H .
CIRCULATION, 1999, 99 (05) :641-648
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