title: Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis.
abstract: Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.
authors: Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brasil, Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors: E
authors: E
authors: Bassi
authors: Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brasil, Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors: M
authors: M
authors: Liberman
authors: Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brasil, Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors: M K
authors: MK
authors: Martinatti
authors: Unidade de Hipertensão, Departamento de Cardiologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brasil, Unidade de Hipertensão, Departamento de Cardiologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors: L A
authors: LA
authors: Bortolotto
authors: Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brasil, Laboratório de Biologia Vascular, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors: F R M
authors: FR
authors: Laurindo
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D001161:Arteriosclerosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003187:Compliance / Q000187:drug effects / Q000502:physiology; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D011817:Rabbits; D013113:Spin Labels; D008063:Thioctic Acid / Q000008:administration & dosage*; D061205:Vascular Calcification / Q000139:chemically induced / Q000517:prevention & control*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D003497:Cyclic N-Oxides; D013113:Spin Labels; D008063:Thioctic Acid; C001803:tempol