Extracellular oxidative damage of vascular walls and their protection using antioxidant enzymes

Abstract

Reactive oxygen species damage blood vessel walls in both initial and subsequent stages of vascular pathology. Oxidative stress contributes to the atherogenic modification of low-density lipoproteins, the development of lipid streaks on the luminal surface, the disturbance of the glycocalyx, and the ulceration and rupture of atherosclerotic plaques. Such a broad spectrum of damaging activity implies the need for both intra-and extracellular protection of vascular walls, which can be realized by the combined use of gene therapy and exogenous biological antioxidants. Recent in vivo studies have shown that modified superoxide dismutase (SOD) and catalase as well as extracellular SOD (an enzyme that employs the specificity of glycosaminoglycan-protein interactions) can be effectively used as antioxidants. Covalent binding of SOD to catalase via the vascular wall glycosaminoglycan (chondroitin sulfate) leads to the formation of a bienzyme conjugate, which exhibits more pronounced antithrombotic activity in vivo in comparison to several other SOD and catalase derivatives. These results point to the importance of the attachment of bioantioxidants to the vascular wall and the conjugation of SOD and catalase activities on this surface. Extracellular bioantioxidants have good prospects for the development of highly effective protectors of vascular walls against oxidative damage in the framework of complex therapy of cardiovascular injury.