Modulation of Oxidant and Antioxidant Enzyme Expression and Function in Vascular Cells

Abstract

Abstract-Pathological conditions that predispose to cardiovascular events, such as hypertension, hypercholesterolemia, and diabetes, are associated with oxidative stress. These observations and further data derived from a plethora of investigations provided accumulating evidence that oxidative stress is decisively involved in the pathogenesis of endothelial dysfunction and atherosclerosis. Several enzymes expressed in vascular tissue contribute to production and efficient degradation of reactive oxygen species, and enhanced activity of oxidant enzymes and/or reduced activity of antioxidant enzymes may cause oxidative stress. Various agonists, pathological conditions, and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase, thioredoxin reductase, and glutathione peroxidase. Data from numerous studies underline the importance of dysregulated oxidant and antioxidant enzymes for the development and progression of atherosclerotic disease in animal models and humans. Specific pharmacological modulation of key enzymes involved in the propagation of oxidative stress rather than using direct antioxidants may be an approach to reduce oxygen radical load in the vasculature and subsequent disease progression in humans. This review focuses on the modulation of expression and activity of major antioxidant and oxidant enzymes expressed in vascular cells.

The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats

“…In vascular cells, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of ROS, and is functionally active within all the layers of the vessel wall [13-15]. In hypertensive patients, vascular smooth muscle cells (VSMCs) from resistance arteries have increased ROS generation, and this increase is linked to NADPH oxidase [16].…”

“…Furthermore, NOX2 mRNA expression in the aorta was found to be greater in SHR compared to the normotensive WKY rats [18]. In vascular cells, SOD is a major cellular antioxidant that provides defence against ·O 2 ˉ [15]. There are three isoforms of SOD which have been identified and include a cytosolic copper/zinc-containing SOD (CuZn-SOD), mitochondrial SOD (Mn-SOD), and extracellular SOD (Ec-SOD).…”

“…There are three isoforms of SOD which have been identified and include a cytosolic copper/zinc-containing SOD (CuZn-SOD), mitochondrial SOD (Mn-SOD), and extracellular SOD (Ec-SOD). The main vascular SOD is Ec-SOD and is produced and secreted by VSMCs [15,16]. Evidence has shown that in atherosclerotic vessels Ec-SOD expression is increased in apoE-deficient mice, a mouse model of atherosclerosis [19].…”

Byproducts of oxidative protein damage and antioxidant enzyme activities in plasma of patients with different degrees of essential hypertension

“…During past several years it has been apparent that a major source of ROS in blood vessels is membrane-associated NADPH oxidase expressed in vasculature, the activation of which is mediated by renin-angiotensin system. 15 On the other hand, decreased activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase) may also contribute to oxidative stress. The experimental data supporting this hypothesis are generally based on measurements of particular intracellular enzymes including red blood cells and mononuclear cells.…”

“…6,16 Although extracellular fluids contain small amounts of antioxidant enzymes, their potential role in the occurance of oxidative stress in EH should not be underestimated. 15 Namely, the failure in the activity of antioxidant enzymes in EH might significantly influence the loss of 'vascular oxidative balance'. However, extracellular enzymatic antioxidant system has not been systematically investigated in EH patients.…”