Calcium cycling proteins in heart failure, cardiomyopathy and arrhythmias

Abstract

A bstractA grow in g b ody o f evidence, includ ing stud ies using genetically engineered m ouse m odels, has show n that C a 2+ cycling and C a 2+ -dependent sign alin g p ath w ays p lay a p ivo tal ro le in card iac hypertrophy and heart failure. In addition, recent stu d ies id en tified th at m u tatio n s o f th e g en es encodin g sarco plasm ic reticu lum (S R ) p rotein s cau se h um an card iom yopathies an d leth al ventricu lar arrhyth m ias. The reg ulatio n of C a 2+ hom eostasis via the SR proteins m ay have potential therapeutic value for heart diseases such as cardiom yopathy, heart failure and arrhythm ias.

Na+–H+ exchanger inhibitor prevents early death in hereditary cardiomyopathy

“…An important characteristic of several types of hypertrophy and congestive heart failure (HF) is a disturbed intracellular calcium ([Ca 2+ ] i ) handling in heart muscles Proschek 1984, 1994;Bkaily and Jacques 1994;Minamisawa et al 2004;Chahine et al 2005). In these pathologies, overload of intracellular Na + ([Na + ] i ) was also reported (Meng and Pierce 1991;Bkaily and Jacques 1994;Karmazyn 2001;Karmazyn et al 2003;Chahine et al 2005;Cingolani and Ennis 2007), which could be due, in part, to an increase in Na + influx caused by upregulation of cardiac Na + -H + exchanger isoform-1 (NHE-1) activity (Meng and Pierce 1991;Karmazyn 2001;Karmazyn et al 2003;Cingolani and Ennis 2007).…”

CPU86017, a berberine derivative, attenuates cardiac failure through normalizing calcium leakage and downregulated phospholamban and exerting antioxidant activity

“…With regards to the treatment of HF, more attention should be paid to the biomarkers of calcium homeostasis in the cardiac cycle [27] . The elevated Ca 2+ levels at the end of diastole that result from calcium leakage are major factors in the pathogenesis of failing hearts.…”

Gene Therapy for Heart Failure

“…The combination of Ca 2+ influx and release raises the free intracellular Ca 2+ concentration, allowing Ca 2+ to bind to the myofilament protein troponin C that then switches on the contractile machinery. [7][8][9][10][11] (Fig. 2).…”

“…Of particular interest is the SERCA2a activity, which is decreased in the failing cardiomyocytes in addition to the decreases of SERCA2a mRNA and protein. 10) Moreover, although the level of PLB expression is unchanged, its phosphorylation state can be altered. 11) This causes an important change in the ratio of PLB to SERCA2a, with its relative increase in the failing heart and the inhibitory effect of PLB being even greater.…”