Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Author(s)

E. Bassi ^[1] ; M. Liberman ^{[2, 1]} ; M.K. Martinatti ^[1] ; L.A. Bortolotto ^[3] ; F.R.M. Laurindo ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Lab Biol Vasc, Inst Coracao INCOR, BR-05403000 Sao Paulo - Brazil

^[2] Hosp Israelita Albert Einstein, Inst Ensino & Pesquisa, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Inst Coracao, Unidade Hipertensao, Dept Cardiol, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 47, n. 2, p. 119-127, 2014-02-00.

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. (AU)

• FAPESP's process: 04/13683-0 - Coupling of stress of endoplasmatic reticule with oxidative stress in vascular cells via interaction between protein disulfide isomerase and NAD(p)H oxidase: role of thiol oxidoredutases
• Grantee: Francisco Rafael Martins Laurindo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
• Grantee: Francisco Rafael Martins Laurindo
• Support Opportunities: Research Projects - Thematic Grants