From mouse to man: understanding heart failure through genetically altered mouse models.
Human heart failure, a complex disease with heterogeneous etiologies, remains one of the most life-threatening diseases known. Identification of "candidate genes" and molecular and biochemical mediators of cardiac hypertrophy and failure has been vigorously pursued to dissect the pathogenesis and signaling pathways of this disease. With the availability of murine cardiac-specific promoters, transgenesis and gene targeting technologies have revolutionized the field of cardiac research. During the past decade, a large number of genetically engineered mouse models with altered cardiac function have been generated. The ability to engineer precise mutations in the heart, coupled with the technological sophistication to quantitate the effects of these mutations on cardiac function at cellular, organ and intact animal levels, has provided novel insights into the molecular mechanisms of heart failure and led to the recognition of a wide array of previously unknown molecular sensors, initiators, transducers, and effectors for the development of cardiac hypertrophy and its transition to heart failure.
Chu
Guoxiang
G
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Haghighi
Kobra
K
Kranias
Evangelia G
EG
D000818:Animals; D002118:Calcium / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology; D003285:Contractile Proteins / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000502:physiology; D004195:Disease Models, Animal; D018390:Gene Targeting; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology
D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D002118:Calcium