Vascular redox

The overall effects of Hey on vascular reactive oxygen species (ROS) generation adversely modulate vascular redox state and activate critical redox-sensitive transcriptional factors such as nuclear-factor kappa B or activator protein-1, which leads to a vicious cycle of inflammation - oxidative stress -endothelial dysfunction favouring vascular disease development. 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

Vascular redox. Is determined by the activity of oxidative sources (NADPH oxidase, uncoupled NOS, xanthine oxidase, etc.) and antioxidant enzymes (superoxide dismutase, glutathione peroxidase) at the vascular wall level. 

I Chen Z, Woodburn KW, Shi C, et al. Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells. Arterioscler 7hromb Vase Biol 2001 21 759-764. 

Ushio-Fukai, M., Alexander, R. W., Akers, M., et al. 1998a. p38 mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy. J Biol Chem 273 15022-15029. 

Zafari, A. M., Ushio-Fukai, M., Minieri, C. A., et al. 1999. Arachidonic acid metabolites mediate angiotensin Il-induced NADH/NADPH oxidase activity and hypertrophy in vascular smooth muscle cells. Antioxidants Redox Signal 1 167-179. 

Zuo, L., Ushio-Fukai, M., Ikeda, S., et al. 2005. Caveolin-1 is essential for activation of Racl and NAD(P)H oxidase after angiotensin II type 1 receptor stimulation in vascular smooth muscle cells role in redox signaling and vascular hypertrophy. Arterioscler Thromb Vase Biol 25 1824-1830. 

Touyz, R.M., Cruzado, M., Tabet, F., Yao, G., Salomon, S., and Schiffrin, E.L. 2003. Redox-dependent MAP kinase signaling by Ang II in vascular smooth muscle cells role of receptor tyrosine kinase transactivation. Can. J. Physiol. Pharmacol. 81 159-167. 

Role of Hyperglycemia and Redox-Induced Signaling in Vascular Complications of Diabetes... 

Blanc, A., N.R. Pandey, and A.K. Srivastava. 2004. Distinct roles of Ca2+, calmodulin, and protein kinase C in Oj-induced activation of ERK1/2, p38 MAPK, and protein kinase B signaling in vascular smooth muscle cells. Antioxid. Redox Signal. 6 353-366. 

Touyz, R.M., G. Yao, E. Viel, F. Amiri, and E.L. Schiffrin. 2004. Angiotensin II and endothelin-1 regulate MAP kinases through different redox-dependent mechanisms in human vascular smooth muscle cells. J. Hypertens. 22 1141-1149. 

Elliott, S.J., and Koliwad, S.K. 1997. Redox control of ion channel activity in vascular endothelial cells by glutathione. Microcirculation 4 341-347. 

Maulik, N., and Das, D.K. 2002. Redox signaling in vascular angiogenesis. Free Radio Biol Med 33 1047-1060. 

Hines, M.E. (1991) The role of certain infauna and vascular plants in the mediation of redox reactions in marine sediments. In Diversity of Environmental Biogeochemistry (Berthelin, J., ed.), pp. 275-286, Elsevier, Amsterdam. 

Compared with plant and other peroxidases, white-rot fungal peroxidases are characterized by their high redox potential, related to the architecture of the heme environment (see Chap. 4). This is required to perform their role in nature, namely the oxidative biodegradation of the recalcitrant lignin polymer present in the cell wall of all vascular plants [30-32], By contrast, one of the roles of plant peroxidases... 

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