The cardiac gap junction: a potential therapeutic target in the treatment of heart disease.
Cardiac gap junctions have been implicated in maintaining cardiac conduction and function. In cardiac disease, expression of connexin 43, the most abundant ventricular gap junction protein, is markedly abnormal, a process termed gap junction remodeling. To date, however, the gap junction has not been directly targeted therapeutically in cardiac disease states. Therefore, we have developed novel and complementary experimental models to investigate whether loss of connexin 43 expression in the heart can be directly linked to the arrhythmic and functional complications of heart disease. In this article, we discuss how data from connexin 43 conditional and chimeric knock-out mice support the hypothesis that gap junction remodeling is a key molecular feature underlying the high incidence of sudden arrhythmic death and exacerbating the ventricular dysfunction associated with acquired heart disease.
Liu
Fangyu
F
Mount Sinai School of Medicine, One East 100th Street, New York, NY 10029, USA.
Gutstein
David E
DE
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D006331:Heart Diseases / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D016276:Ventricular Function / Q000502:physiology
D018031:Connexin 43; D017630:Connexins