[Calcium kinetics in the progression of heart failure].
The heart has the basic function of pumping blood continuously to the whole body, alternating periods of systole, when it ejects blood, with periods of diastole, when it fills. These mechanical phenomena are strictly regulated by cardiomyocyte physiology, in which calcium (Ca2+) kinetics has a critical role. In fact, Ca2+ influx during the action potential and consequent Ca2+ outflow from the sarcoplasmic reticulum (SR) are essential for myofilament activation--excitation-contraction coupling--whereas Ca2+ reuptake to the SR and extracellular space is crucial for relaxation--inactivation-relaxation coupling. However, it is known that in heart failure progression the expression of genes that code for proteins involved in the regulation of cardiomyocyte Ca2+ homeostasis is profoundly disturbed. In particular, the decreased expression of SERCA2a, the main protein implicated in Ca2+ reuptake during relaxation, is established in the failing human heart. These molecular disturbances lead to cardiomyocyte contractile failure and to systolic and diastolic dysfunction of the heart. The functional and molecular characterization of heart failure progression enables a better understanding of its pathophysiology and the definition of new therapeutic targets. Recent in-vitro and in-vivo experiments have demonstrated that SERCA2a gene transfer can reverse or impede the contractile dysfunction of heart failure progression. In this context, and given the current limitations in the treatment of this disease, evaluation of the clinical impact of these new therapeutic strategies is warranted.
Roncon-Albuquerque Júnior
Roberto
R
Serviço de Fisiopatologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Leite-Moreira
Adelino F
AF
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D018450:Disease Progression; D015316:Genetic Therapy; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism
D015220:Calcium Channels; D002118:Calcium