title: Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis.
abstract: BACKGROUND
  The progression of aortic stenosis (AS) has been shown to be faster in patients with the metabolic syndrome. We sought to determine the relationships between blood pressure, inflammation, oxidative stress and valvular inflammation in a population of normotensive and prehypertensive patients with AS.
  
  
  METHODS
  In this study, 36 male patients (age: 61.5±2 years) with AS undergoing an aortic valve replacement were investigated. Plasma levels of adiponectin, oxidized-LDL (ox-LDL), angiotensinogen (AGN) and angiotensin I-II (Ang I-II) were measured. On explanted aortic valves, immunohistochemistry studies and quantitative PCR (q-PCR) analyses were performed to document the expression of inflammatory cytokines.
  
  
  RESULTS
  Systolic blood pressure (SBP) was positively correlated with plasma level of ox-LDL (r=0.4; p=0.02), AGN (r=0.41; p=0.01), and white blood cells count (r=0.33; p=0.04), whereas it was inversely related to plasma level of adiponectin (r=-.35; p=0.04). After adjustment for covariates, plasma level of ox-LDL (p=0.01) remained significantly associated with SBP (p=0.01). Within the aortic valve, expression of TNF-α was significantly associated with plasma levels of ox-LDL (r=0.58; p=0.03), Ang II (r=0.69; p=0.013), and waist circumference (r=0.60; p=0.02), whereas valvular expression of IL-6 was associated with plasma level of Ang II (r=0.51; p=0.03). In explanted AS valves, ox-LDL was documented near calcified areas and colocalized with Ang II, IL-6, and TNF-α.
  
  
  CONCLUSIONS
  Conditions associated with a higher oxidative stress and activation of the renin angiotensin system, such as encountered in viscerally obese and prehypertensive patients, contribute to higher valvular inflammation in AS.
authors.affiliation: Laboratoire d'Études Moléculaires des Valvulopathies (LEMV), Laval Hospital Research Center/Quebec Heart Institute, Department of Surgery, Laval University, Québec, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Côté
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
authors.forename: Andrée
authors.initials: A
authors.lastname: Pépin
authors.forename: Dominique
authors.initials: D
authors.lastname: Fournier
authors.forename: Audrey
authors.initials: A
authors.lastname: Audet
authors.forename: Benoît
authors.initials: B
authors.lastname: Arsenault
authors.forename: Christian
authors.initials: C
authors.lastname: Couture
authors.forename: Paul
authors.initials: P
authors.lastname: Poirier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
mesh_terms: D052242:Adiponectin / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D000808:Angiotensinogen / Q000097:blood; D001024:Aortic Valve Stenosis / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress / Q000276:immunology; D058246:Prehypertension / Q000276:immunology / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D055105:Waist Circumference / Q000502:physiology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I