title: Partial nephrectomy as a model for uremic cardiomyopathy in the mouse.
abstract: Because of the plethora of genetic manipulations available in the mouse, we performed a partial nephrectomy in the mouse and examined whether the phenotypical features of uremic cardiomyopathy described in humans and rats were also present in the murine model. A 5/6 nephrectomy was performed using a combination of electrocautory to decrease renal mass on the left kidney and right surgical nephrectomy. This procedure produced substantial and persistent hypertension as well as increases in circulating concentrations of marinobufagenin. Invasive physiological measurements of cardiac function demonstrated that the 5/6 nephrectomy resulted in impairment of both active and passive left ventricular relaxation at 4 wk whereas tissue Doppler imaging detected changes in diastolic function after 6 wk. Morphologically, hearts demonstrated enlargement and progressive fibrosis, and biochemical measurements demonstrated downregulation of the sarcoplasmic reticulum calcium ATPase as well as increases in collagen-1, fibronectin, and vimentin expression. Our results suggest that partial nephrectomy in the mouse establishes a model of uremic cardiomyopathy which shares phenotypical features with the rat model as well as patients with chronic renal failure.
authors.affiliation: Department of Medicine, University of Toledo College of Medicine, Toledo, OH 43614-5809, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Jihad
authors.initials: J
authors.lastname: Elkareh
authors.forename: Amjad
authors.initials: A
authors.lastname: Shidyak
authors.forename: Anna P
authors.initials: AP
authors.lastname: Shapiro
authors.forename: Sleiman
authors.initials: S
authors.lastname: Smaili
authors.forename: Krishna
authors.initials: K
authors.lastname: Mutgi
authors.forename: Shalini
authors.initials: S
authors.lastname: Gupta
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Eric
authors.initials: E
authors.lastname: Morgan
authors.forename: Samer
authors.initials: S
authors.lastname: Khouri
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cooper
authors.forename: Sankaridrug M
authors.initials: SM
authors.lastname: Periyasamy
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.forename: Olga V
authors.initials: OV
authors.lastname: Fedorova
authors.forename: Alexei Y
authors.initials: AY
authors.lastname: Bagrov
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002018:Bufanolides / Q000097:blood; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy; D051437:Renal Insufficiency / Q000150:complications*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D002018:Bufanolides; C093896:marinobufagenin; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase