Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis.
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.
Côté
Nancy
N
Laboratoire d'Études Moléculaires des Valvulopathies (LEMV), Laval Hospital Research Center/Quebec Heart Institute, Department of Surgery, Laval University, Québec, Canada.
Pibarot
Philippe
P
Pépin
Andrée
A
Fournier
Dominique
D
Audet
Audrey
A
Arsenault
Benoît
B
Couture
Christian
C
Poirier
Paul
P
Després
Jean-Pierre
JP
Mathieu
Patrick
P
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
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