Targeting calcium cycling proteins in heart failure through gene transfer.
Our understanding of cardiac excitation-contraction coupling has improved significantly over the last 10 years. Furthermore, defects in the various steps of excitation-contraction coupling that characterize cardiac dysfunction have been identified in human and experimental models of heart failure. The various abnormalities in ionic channels, transporters, kinases and various signalling pathways collectively contribute to the 'failing phenotype.' However, deciphering the causative changes continues to be a challenge. An important tool in dissecting the importance of the various changes in heart failure has been the use of cardiac gene transfer. To achieve effective cardiac gene transfer a number of obstacles remain, including appropriate vectors for gene delivery, appropriate delivery systems, and a better understanding of the biology of the disease. In this review, we will examine our current understanding of these various factors. Gene transfer provides not only a potential therapeutic modality but also an approach to identifying and validating molecular targets.
del Monte
Federica
F
Program in Cardiovascular Gene Therapy, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Hajjar
Roger J
RJ
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002303:Cardiac Output, Low / Q000378:metabolism*; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D002135:Calcium-Binding Proteins; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases