OBJECTIVE: To determine whether differences exist in valvular high density lipoprotein (HDL) content between non-stenotic and stenotic aortic valves, and whether HDL could retard valvular calcification locally. METHODS: Stenotic aortic valves were obtained from valve replacement surgery and non-stenotic control valves from cardiac transplantations or at autopsy. The valvular localization and concentration of apolipoproteinA-I (apoA-I) were analyzed by immunohistochemistry and ELISA. The effects of HDL on the secretion of calcifying mediators and proinflammatory cytokines by cultured aortic valve myofibroblasts were assessed by ELISA and real-time PCR. RESULTS: The concentration of apoA-I was higher in control than in stenotic valves (p < 0.05). ApoA-I surrounded the calcific deposits in stenotic valves, co-localizing with apoB, apoE, and osteoprotegerin (OPG). Incubation of cultured valve myofibroblasts with HDL increased their secretion of OPG (p < 0.001). Furthermore, incubation of myofibroblasts with HDL led to decreased mRNA expression of tumor necrosis factor alpha (TNF-α) (p < 0.05). CONCLUSIONS: The amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-α in vitro. Since OPG is known to inhibit and TNF-α to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves.
OBJECTIVE: To determine whether differences exist in valvular high density lipoprotein (HDL) content between non-stenotic and stenotic aortic valves, and whether HDL could retard valvular calcification locally. METHODS: Stenotic aortic valves were obtained from valve replacement surgery and non-stenotic control valves from cardiac transplantations or at autopsy. The valvular localization and concentration of apolipoproteinA-I (apoA-I) were analyzed by immunohistochemistry and ELISA. The effects of HDL on the secretion of calcifying mediators and proinflammatory cytokines by cultured aortic valve myofibroblasts were assessed by ELISA and real-time PCR. RESULTS: The concentration of apoA-I was higher in control than in stenotic valves (p < 0.05). ApoA-I surrounded the calcific deposits in stenotic valves, co-localizing with apoB, apoE, and osteoprotegerin (OPG). Incubation of cultured valve myofibroblasts with HDL increased their secretion of OPG (p < 0.001). Furthermore, incubation of myofibroblasts with HDL led to decreased mRNA expression of tumor necrosis factor alpha (TNF-α) (p < 0.05). CONCLUSIONS: The amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-α in vitro. Since OPG is known to inhibit and TNF-α to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves.
Authors: Anna E Bortnick; Petra Buzkova; James D Otvos; Majken K Jensen; Michael Y Tsai; Matthew J Budoff; Rachel H Mackey; Samar R El Khoudary; Elda Favari; Ryung S Kim; Carlos J Rodriguez; George Thanassoulis; Jorge R Kizer Journal: Arterioscler Thromb Vasc Biol Date: 2022-08-18 Impact factor: 10.514
Authors: J Trapeaux; D Busseuil; Y Shi; S Nobari; D Shustik; M Mecteau; I El-Hamamsy; M Lebel; R Mongrain; E Rhéaume; J-C Tardif Journal: Br J Pharmacol Date: 2013-08 Impact factor: 8.739
Authors: María Luna-Luna; David Cruz-Robles; Nydia Ávila-Vanzzini; Valentín Herrera-Alarcón; Jesús Martínez-Reding; Sergio Criales-Vera; Julio Sandoval-Zárate; Jesús Vargas-Barrón; Carlos Martínez-Sánchez; Armando Roberto Tovar-Palacio; José Manuel Fragoso; Elizabeth Carreón-Torres; Gilberto Vargas-Alarcón; Óscar Pérez-Méndez Journal: Lipids Health Dis Date: 2017-08-18 Impact factor: 3.876
Authors: Satu Lehti; Reijo Käkelä; Sohvi Hörkkö; Outi Kummu; Satu Helske-Suihko; Markku Kupari; Kalervo Werkkala; Petri T Kovanen; Katariina Oörni Journal: PLoS One Date: 2013-06-07 Impact factor: 3.240