Redox Processes Underlying the Vascular Repair Reaction

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.

Can a Strychnos species be used as antiulcer agent? Ulcer healing action from alkaloid fraction of Strychnos pseudoquina St. Hil. (Loganiaceae)

“…)/day of methanolic extract (ME) or alkaloid fraction (EAF) from Strychnos pseudoquina administered for 14 consecutive days after ulcer formation (n = 7-8 mucosa by proliferating vessels in gastric mucosa that stimulated cell proliferation in the healing region. Leite et al (2004) observed that replenishment of SOD (superoxide dismutase) led to decrease in constrictive remodeling and enhanced angiogenesis. SOD is the most important enzymes responsible for eliminating free radicals from the cell, given that it transforms O 2 •− radicals into H 2 O 2 and protects the cells from damage through the removal of those radicals.…”

Interfacial biology of in-stent restenosis

“…This degradation is inhibited by the activity of the superoxide dismutase enzyme, as well as by metal ion chelators and the metal ion-binding protein bovine serum albumin. The activation of enzymes such as NADPH oxidase significantly increases the generation of superoxide species [55]. In particular, after stent deployment, the amount of superoxide released is higher as compared with balloon injury, and the activity of vascular superoxide dismutases exhibits a sustained decrease following injury.…”

“…In particular, after stent deployment, the amount of superoxide released is higher as compared with balloon injury, and the activity of vascular superoxide dismutases exhibits a sustained decrease following injury. Although the release of these highly reactive free radicals is proportional to the degree of injury, it rapidly subsides in the phases following the injury [55].…”

Nitration Transforms a Sensitive Peroxiredoxin 2 into a More Active and Robust Peroxidase

“…Nitration of tyrosine residues has an impact on protein structure and activity (in general, inactivation, although a gain of function has also been reported) and is linked to a variety of pathological conditions such as neurodegenerative and cardiovascular diseases (56,57). Nitration of typical 2-Cys Prx has been reported in vitro and in vivo (20,47,58).…”