title: Monocyte chemoattractant proteins mediate myocardial microvascular dysfunction in swine renovascular hypertension.
abstract: BACKGROUND
  Monocyte chemoattractant proteins (MCPs) play an important role in mediating inflammatory processes. Hypertension (HTN) is associated with inflammation as well as impaired cardiac microcirculatory function and structure, but the contribution of MCPs to these alterations remained unclear. This study tested the hypothesis that MCPs regulate cardiac microvascular function and structure in experimental HTN.
  
  
  RESULTS
  Pigs (n=6 per group) were studied after 10 weeks of normal, renovascular HTN, or renovascular HTN+ bindarit (MCPs inhibitor, 50 mg/kg/d PO). Left ventricular (LV) function, myocardial microvascular permeability, and fractional vascular volume were assessed by fast computed tomography before and after adenosine infusion (400 microg/kg/min). Myocardial fibrosis, inflammation, and microvascular remodeling were determined ex vivo. Hypertension was not altered by bindarit, but LV hypertrophy and diastolic function were improved. In response to adenosine, myocardial microvascular permeability increased in HTN (from 0.0083+/-0.0009 to 0.0103+/-0.0011 AU, P=0.038 versus baseline) and fractional vascular volume decreased, whereas both remained unchanged in normal and HTN+bindarit pigs. HTN upregulated endothelin-1 expression, myocardial inflammation, and microvascular wall thickening, which were inhibited by bindarit.
  
  
  CONCLUSIONS
  MCPs partly mediate myocardial inflammation, fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension. Inhibition of MCPs could potentially be a therapeutic target in hypertensive cardiomyopathy.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhu
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.forename: Ronit
authors.initials: R
authors.lastname: Lavi
authors.forename: Elena
authors.initials: E
authors.lastname: Daghini
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Gibson
authors.forename: Angelo
authors.initials: A
authors.lastname: Guglielmotti
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D003097:Collateral Circulation / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011336:Probability; D011897:Random Allocation; D034421:Sus scrofa; D013552:Swine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D018945:Monocyte Chemoattractant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C417249:collagenase 1