title: Microvascular abnormalities in adjuvant-induced arthritis: relationship to macrovascular endothelial function and markers of endothelial activation.
abstract: OBJECTIVE
  To determine the time course of microvascular abnormalities and the link with macrovascular endothelial function and circulating markers of endothelial activation in adjuvant-induced arthritis (AIA) in rats.
  
  
  METHODS
  Microvascular function/structure and mechanics were studied in third-order mesenteric arteries subjected to flow and/or pressure on day 4 (preclinical arthritis), day 11 (very early arthritis), day 33 (severe disease), and day 90 (when inflammation has resolved) after AIA induction. Macrovascular function was studied in aortic rings, and blood pressure, plasma levels of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at each time point.
  
  
  RESULTS
  Mesenteric flow-mediated vasodilation was significantly reduced from very early arthritis to chronic disease, whereas increased microvascular arterial stiffness was evident only on day 33. Macrovascular endothelial dysfunction was observed only on day 33. Thus, on day 90, whereas rats with AIA recovered normal macrovascular endothelial function, microvascular endothelial function remained impaired. No correlation was found between micro- and macrovascular endothelial function throughout the course of arthritis (r = 0.180, P = 0.229). Furthermore, no correlation was found between CRP levels, ICAM-1 levels, and endothelial function whatever the vascular bed. AIA was not associated with change in blood pressure or VCAM levels.
  
  
  CONCLUSIONS
  Our findings indicate that microvascular endothelial dysfunction occurs earlier than macrovascular endothelial dysfunction and microvascular arterial stiffness during arthritis, suggesting that microvascular endothelial function would be a valuable tool for the early assessment of cardiovascular risk in RA. Neither the ICAM-1 level nor the CRP level is a good marker of micro- or macrovascular endothelial dysfunction.
authors.affiliation: EA 4267, FHU INCREASE, Besançon, France.
authors.forename: Perle
authors.initials: P
authors.lastname: Totoson
authors.forename: Katy
authors.initials: K
authors.lastname: Maguin-Gaté
authors.forename: Maude
authors.initials: M
authors.lastname: Nappey
authors.forename: Clément
authors.initials: C
authors.lastname: Prati
authors.forename: Daniel
authors.initials: D
authors.lastname: Wendling
authors.forename: Céline
authors.initials: C
authors.lastname: Demougeot
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005620:Freund's Adjuvant; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism* / Q000503:physiopathology; D055806:Microvessels / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D059289:Vascular Stiffness / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D005620:Freund's Adjuvant