OBJECTIVE: Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved. METHODS AND RESULTS: We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tg rabbits, and high-density lipoproteins of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tg rabbits. In addition, β-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than β-very-low-density lipoproteins of non-Tg rabbits. CONCLUSIONS: These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.
OBJECTIVE:Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved. METHODS AND RESULTS: We compared the susceptibility of humanapo A-IItransgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tgrabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tgrabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tgrabbits, and high-density lipoproteins of Tgrabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tgrabbits. In addition, β-very-low-density lipoproteins of Tgrabbits were less sensitive to copper-induced oxidation than β-very-low-density lipoproteins of non-Tgrabbits. CONCLUSIONS: These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.
Authors: M C de Beer; D M Durbin; L Cai; N Mirocha; A Jonas; N R Webb; F C de Beer; D R van Der Westhuyzen Journal: J Biol Chem Date: 2001-02-09 Impact factor: 5.157
Authors: J E Buring; G T O'Connor; S Z Goldhaber; B Rosner; P N Herbert; C B Blum; J L Breslow; C H Hennekens Journal: Circulation Date: 1992-01 Impact factor: 29.690
Authors: Vicent Ribas; José Luis Sánchez-Quesada; Rosa Antón; Mercedes Camacho; Josep Julve; Joan Carles Escolà-Gil; Luís Vila; Jordi Ordóñez-Llanos; Francisco Blanco-Vaca Journal: Circ Res Date: 2004-09-23 Impact factor: 17.367
Authors: Sara Fernández-Castillejo; Laura Rubió; Álvaro Hernáez; Úrsula Catalán; Anna Pedret; Rosa-M Valls; Juana I Mosele; Maria-Isabel Covas; Alan T Remaley; Olga Castañer; Maria-José Motilva; Rosa Solá Journal: Mol Nutr Food Res Date: 2017-10-26 Impact factor: 5.914