on November 1, 2007
Published online before print November 1, 2007, doi: 10.1161/ATVBAHA.107.154989
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Submitted on March 15, 2007
Accepted on October 22, 2007
Association Between Plasma LDL Particle Size, Valvular Accumulation of Oxidized LDL, and Inflammation in Patients With Aortic Stenosis
Dania Mohty ;
From the Laboratoire d’Études Moléculaires des Valvulopathies (LEMV) (D.M., C. Côté, P.M.), Groupe de Recherche en Valvulopathies (GRV), Laval Hospital Research Center/Quebec Heart Institute, Department of Surgery, Laval University, Quebec, Canada; the Department of Medicine (D.M., P.P.), Laval University, Quebec, Canada; the Division of Kinesiology (J.-P.D., B.A., A.C.), Department of Social and Preventive Medicine, Laval University, Québec, Canada; UMR CNRS 6542 (P.C.), Université François Rabelais, Tours, France; and the Department of Pathology (C. Couture), Laval Hospital, Quebec, Canada.
* To whom correspondence should be addressed. E-mail: patrick.mathieu{at}chg.ulaval.
Objective—In patients with severe aortic stenosis (AS), we examine the association between: (1) the content of oxidized LDL (oxLDL) in the aortic valve and the degree of inflammation and remodeling; (2) The proportion of small dense LDL particles in the plasma and the presence of oxLDL in the valve along with hemodynamic progression of valve stenosis.
Methods and Results—We have examined 102 explanted AS valves. Tissue remodeling, inflammation, and accumulation of oxLDL were determined. A complete plasma lipid profile including the measurement of the relative proportion of small low-density lipoprotein (%LDL<255Å) was obtained. Valves with higher oxLDL content had a significantly higher density of inflammatory cells, expression of tumor necrosis factor (TNF)-
, and increased tissue remodeling score. The %LDL<255Å was significantly associated with oxLDL score within the aortic valve. In a subset of 59 patients in whom stenosis progression was measured, the %LDL<255Å correlated with the annualized peak gradient (r=0.29; P=0.04).
Conclusion—Increased proportion of circulating small dense LDL particles is associated with faster progression rate of stenosis and greater accumulation of oxLDL in the aortic valve. These findings suggest that therapeutic interventions aimed at lowering the production of small dense LDL particles in patients with AS might represent a potentially interesting therapeutic avenue.
Key words: aortic stenosis • oxidized low-density lipoproteins • small size low-density lipoprotein particles
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