title: Arterial stiffness is associated with increased monocyte expression of adiponectin receptor mRNA and protein in patients with coronary artery disease.
abstract: BACKGROUND
  Arterial stiffness and carotid intima-media thickness (IMT) constitute validated cardiovascular prognostic markers. Adiponectin and its receptors 1 (AdipoR1) and 2 (AdipoR2) are involved in coronary artery disease (CAD). We investigated whether AdipoR1 and R2 mRNA and protein expression are associated with arterial stiffness, IMT and extent of coronary atherosclerosis.
  
  
  METHODS
  We studied 71 patients (61 men, 10 women) with angiographically proven CAD. We measured: (i) monocyte expression of AdipoR1 and AdipoR2 mRNA (quantitative real-time PCR) and protein expression (flow cytometry) (iii) adiponectin, metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) blood levels, (iv) carotid-femoral artery pulse wave velocity (PWV) and carotid IMT.
  
  
  RESULTS
  Patients with multi-vessel CAD had higher AdipoR1 and AdipoR2 mRNA than those with single-vessel (P < 0.05). PWV was associated with AdipoR1 mRNA (r = 0.474), AdipoR1 protein (r = 0.228), AdipoR2 mRNA (r = 0.716), AdipoR2-protein (r = 0.261), adiponectin (r = 0.236), and MMP-9 (r = 0.350) (P < 0.05, for all correlations). After adjustment for age, sex, waist-hip ratio, and mean blood pressure both AdipoR1 and AdipoR2 mRNA remained independent determinants of PWV (R(2) = 0.35 and R(2) = 0.57, P < 0.05). IMT was also associated with AdipoR2 mRNA, AdipoR2 protein, and MMP-9 (P < 0.05). Increased expression of ADR2 mRNA significantly related to MMP-9 (r = 0.210), and CRP (r = 0.531) (P < 0.05).
  
  
  CONCLUSIONS
  Increased mRNA and protein expression of adiponectin receptors is related with increased aortic stiffness, coronary and peripheral atherosclerosis in patients with CAD. The interrelation of AdipoR2 with inflammatory markers, PWV and IMT suggests a compensatory increase of these receptors to counteract the excess inflammatory and atherogenic process in CAD. Thus, adiponectin receptors may provide a potential therapeutic target of agents activating their beneficial action.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.42.
authors.affiliation: 2nd Cardiology Department, Medical School, University of Athens, Attikon University General Hospital, Athens, Greece. ignoik@otenet.gr
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kadoglou
authors.forename: Panayoula C
authors.initials: PC
authors.lastname: Tsiotra
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kollias
authors.forename: Ioannis
authors.initials: I
authors.lastname: Palios
authors.forename: Katerina
authors.initials: K
authors.lastname: Fountoulaki
authors.forename: Iosif
authors.initials: I
authors.lastname: Halvatsiotis
authors.forename: Eirini
authors.initials: E
authors.lastname: Maratou
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: John
authors.initials: J
authors.lastname: Lekakis
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Raptis
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D003935:Diagnostic Techniques, Cardiovascular; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics*; D059289:Vascular Stiffness; D049629:Waist-Hip Ratio
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9