title: Selective improvement in renal function preserved remote myocardial microvascular integrity and architecture in experimental renovascular disease.
abstract: OBJECTIVE
  Atherosclerotic renovascular disease (ARVD) may impair renal function and increase cardiovascular morbidity and mortality, but the mechanism by which ARVD impacts cardiovascular function is unclear. We tested the hypothesis that preservation of renal function can reverse cardiac dysfunction in ARVD.
  
  
  RESULTS
  Endothelial progenitor cells (EPC) were injected intra-renally (ARVD+EPC) after 6 weeks of swine ARVD (concurrent hypercholesterolemia and renovascular hypertension), and single-kidney function and myocardial blood-flow and microvascular permeability (MP) responses to adenosine were assessed using CT 4 weeks later. Myocardial microvascular density was evaluated by micro-CT. Inflammation and oxidative-stress were assessed in kidney venous and systemic blood samples. Normal and untreated ARVD pigs served as controls. Blood pressure was similarly increased in ARVD and ARVD+EPC. Compared to normal, ARVD showed lower glomerular filtration rate, elevated renal vein and systemic oxidized LDL (ox-LDL), aldosterone, uric acid, isoprostanes, transforming growth factor (TGF)-β, and interleukine-6. Renal vein ox-LDL and TGF-β showed a positive gradient across the stenotic kidney, indicating increased renal oxidative stress and fibrogenic activity. Furthermore, ARVD impaired myocardial blood-flow and MP response to adenosine, decreased microvascular density, and induced myocardial fibrosis. Improvement of renal function in ARVD+EPC decreased systemic aldosterone, inflammation, and oxidative stress, and improved myocardial microvascular integrity and density.
  
  
  CONCLUSIONS
  Selective improvement in renal function, which reduced renal and systemic oxidative stress and inflammation, preserved remote myocardial microvascular function and architecture, despite enduring hypertension. These findings underscore functionally important cardiorenal crosstalk possibly mediated by renal injury signals.
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Urbieta-Caceres
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Kyle
authors.initials: K
authors.lastname: Textor
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002199:Capillary Permeability; D002302:Cardiac Output; D002404:Catheterization / Q000009:adverse effects; D002478:Cells, Cultured; D003326:Coronary Circulation; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000637:transplantation*; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006331:Heart Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006937:Hypercholesterolemia / Q000150:complications / Q000209:etiology; D006978:Hypertension, Renovascular / Q000209:etiology / Q000503:physiopathology / Q000601:surgery; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery*; D008833:Microcirculation; D055806:Microvessels / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D012078:Renal Artery Obstruction / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators