title: Hypertrophy signaling pathways in experimental chronic aortic regurgitation.
abstract: The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.
authors.affiliation: Division of Cardiology, Johns Hopkins Medical Institutions, 600 N Wolfe St., Carnegie 568, Baltimore, MD, 21287, USA.
authors.forename: Niels Thue
authors.initials: NT
authors.lastname: Olsen
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Dimaano
authors.forename: Thomas
authors.initials: T
authors.lastname: Fritz-Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Sogaard
authors.forename: Khalid
authors.initials: K
authors.lastname: Chakir
authors.forename: Kristian
authors.initials: K
authors.lastname: Eskesen
authors.forename: Charles
authors.initials: C
authors.lastname: Steenbergen
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001022:Aortic Valve Insufficiency / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D018618:Echocardiography, Doppler, Color; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D009320:Atrial Natriuretic Factor; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin