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Redox Processes Underlying the Vascular Repair Reaction

  • World Progress in Surgery
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Abstract

Accumulating evidence indicates that vascular dysfunction in atherosclerosis, hypertension, and diabetes is either caused by or accompanied by oxidative stress in the vessel wall. In particular, the role of redox processes as mediators of vascular repair and contributors to post-angioplasty restenosis is increasingly evident. Yet the pathophysiology of such complex phenomena is still unclear. After vascular injury, activation of enzymes such as NADPH oxidase leads to a marked increase in superoxide generation, proportional to the degree of injury, which rapidly subsides. Such early superoxide production is significantly greater after stent deployment, as compared to balloon injury. Recent data suggest the persistence of low levels of oxidant stress during the vascular repair reaction in neointimal and medial layers. Despite the compensatory increase in expression of iNOS and nNOS, nitric oxide bioavailability is reduced because of increased reaction rates with superoxide, yielding as by-products reactive nitrogen/oxygen species that induce protein nitration. Concurrently, the activity of vascular superoxide dismutases exhibits a sustained decrease following injury. This decreased activity appears to be a key contributor to vasoconstrictive remodeling and a major determinant of the occurrence of nitrative/oxidative stress. Replenishment of superoxide dismutase (SOD), as well as treatment with vitamins C and E or the lipid-lowering drug probucol and its analogs, led to decrease in constrictive remodeling and improved vessel caliber. Better understanding of the redox pathophysiology of vascular repair should help clarify the pathogenesis of many other vascular conditions and may provide novel therapeutic strategies to prevent vascular lumen loss.

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Acknowledgments.

Work from our laboratory was supported by FAPESP, FINEP/Pronex, and Fundação Zerbini.

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  1. Vascular Biology Laboratory, Heart Institute (INCOR), University of São Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar, 44 – Cerqueira, César SP 05403-000, São Paulo, Brazil

    Paulo F. Leite M.D., Ph.D., Marcel Liberman M.D., Fábio Sandoli de Brito M.D., Ph.D. & Francisco R.M. Laurindo M.D., Ph.D.

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  1. Paulo F. Leite M.D., Ph.D.
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Correspondence to Francisco R.M. Laurindo M.D., Ph.D..

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Leite, P., Liberman, M., Sandoli de Brito, F. et al. Redox Processes Underlying the Vascular Repair Reaction. World J. Surg. 28, 331–336 (2004). https://doi.org/10.1007/s00268-003-7399-4

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