RESUMO
Gene therapy as a therapeutic strategy for Heart Failure, is an area that within the last 10 years has experienced an important increase in research, becoming one of the most promising areas to obtain a successful therapy for heart failure due to the possibility of correcting the basic defects observed at the cellular level in this pathology. One of the first things to consider on the use of this therapy is the way to deliver the genetic material, Adenovirus, and Adeno-associated virus, have shown the best capabilities in the myocardium; the delivery by local means has shown best results when compared with peripheral administration. Multiple physiopathological mechanisms susceptible of modifying by gene therapy have been identified, including the regulation of Ca2+ fluxes during excitation-contraction coupling, altered intracellular signalling, and adrenergic system, blockade of apoptosis and angiogenesis. The objective of this review, is to made a recount about the status of the literature and analyze future perspectives for gene therapy.
Assuntos
Humanos , Terapia Genética , Insuficiência Cardíaca , Técnicas de Transferência de Genes , Vetores Genéticos , Terapia Genética/métodosRESUMO
The sarcoplasmic reticulum (SR) constitutes the main intracellular calcium store in striated muscle and plays an important role in the regulation of excitation-contraction-coupling (ECC) and of intracellular calcium concentrations during contraction and relaxation. The regulation of ECC occurs due to the interaction among the main proteins of the SR that are the calcium release channel or ryanodine receptor, the Ca2+-ATPase, phospholamban and calsequestrin. Due to the importance of ECC in the physiopathology of a number of cardiac diseases, the role of the SR and its components has been widely investigated in some pathologies, specifically cardiac hypertrophy, heart failure, and hereditary arrhythmias. Therefore, the SR proteins constitute an area of research of great interest for the development of new genetic and pharmacologic therapies; from this derives the importance of understanding the function of the SR. This review analyzes the expression, structure, and function of the main SR proteins, their role on myocardial contraction and relaxation and in the changes that occur in cardiac pathologies.