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(<255A)) was obtained. Valves with higher oxLDL content had a significantly higher density of inflammatory cells, expression of tumor necrosis factor (TNF)-alpha, and increased tissue remodeling score. The %LDL(<255A) was significantly associated with oxLDL score within the aortic valve. In a subset of 59 patients in whom stenosis progression was measured, the %LDL(<255A) correlated with the annualized peak gradient (r=0.29; P=0.04). CONCLUSIONS: 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.
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(<255A)) was obtained. Valves with higher oxLDL content had a significantly higher density of inflammatory cells, expression of tumor necrosis factor (TNF)-alpha, and increased tissue remodeling score. The %LDL(<255A) was significantly associated with oxLDL score within the aortic valve. In a subset of 59 patients in whom stenosis progression was measured, the %LDL(<255A) correlated with the annualized peak gradient (r=0.29; P=0.04). CONCLUSIONS: 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.
Authors: Neris Dincer; Tuncay Dagel; Baris Afsar; Adrian Covic; Alberto Ortiz; Mehmet Kanbay Journal: Int Urol Nephrol Date: 2018-12-05 Impact factor: 2.370
Authors: Jia Teng Sun; Yuan Yuan Chen; Jing Yan Mao; Yan Ping Wang; Ya Fen Chen; Xiang Hu; Ke Yang; Yan Liu Journal: J Cardiovasc Transl Res Date: 2019-07-31 Impact factor: 4.132
Authors: Aeron Small; Daniel Kiss; Jay Giri; Saif Anwaruddin; Hasan Siddiqi; Marie Guerraty; Julio A Chirinos; Giovanni Ferrari; Daniel J Rader Journal: Arterioscler Thromb Vasc Biol Date: 2017-02-02 Impact factor: 8.311