title: Myocardial infarction impairs renal function, induces renal interstitial fibrosis, and increases renal KIM-1 expression: implications for cardiorenal syndrome.
abstract: Progressive decline in renal function coexists with myocardial infarction (MI); however, little is known about its pathophysiology. This study aimed to systematically identify post-MI renal changes (functional, histological, and molecular) over time in a rat MI model and examine potential mechanisms that may underlie these changes. Rats were randomized into three groups: nonoperated, sham, and MI. Cardiac and renal function was assessed before death at 1, 4, 8, 12, and 16 wk with tissues collected for histological, protein, and gene studies. Tail-cuff blood pressure was lower in MI than sham and nonoperated animals only at 1 wk (P < 0.05). Systolic function was reduced (P < 0.0001) while heart/body weight and left ventricle/body weight were significantly greater in MI animals at all time points. Glomerular filtration rate decreased following MI at 1 and 4 wk (P < 0.05) but not at 8 and 12 wk and then deteriorated further at 16 wk (P = 0.052). Increased IL-6 gene and transforming growth factor (TGF)-β protein expression as well as macrophage infiltration in kidney cortex was detected at 1 wk (P < 0.05). Renal cortical interstitial fibrosis was significantly greater in MI animals from 4 wk, while TGF-β bioactivity (phospho-Smad2) was upregulated at all time points. The degree of fibrosis increased and was maximal at 16 wk. In addition, kidney injury molecule-1-positive staining in the tubules was more prominent in MI animals, maximal at 1 wk. In conclusion, renal impairment occurs early post-MI and is associated with hemodynamic and structural changes in the kidney possibly via activation of the Smad2 signaling pathway.
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. henry.krum@monash.edu
authors.forename: Suree
authors.initials: S
authors.lastname: Lekawanvijit
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kompa
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bing H
authors.initials: BH
authors.lastname: Wang
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D059347:Cardio-Renal Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C110936:Havcr1 protein, rat; C497784:Smad2 protein, rat