Vascular Protection

Abstract

Abstract-Blood vessels express 3 isoforms of superoxide dismutase (SOD): cytosolic or copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD) localized in mitochondria, and an extracellular form of CuZn-SOD (EC-SOD). Because there are no selective pharmacological inhibitors of individual SOD isoforms, the functional importance of the different SODs has been difficult to define. Recent molecular approaches, primarily the use of genetically-altered mice and viral-mediated gene transfer, have allowed investigators to begin to define the role of specific SOD isoforms in vascular biology. This review will focus mainly on the role of individual SODs in relation to endothelium under normal conditions and in disease states. This area is important because reactive oxygen species and superoxide anion are thought to play major roles in changes in vascular structure and function in pathophysiology. Key Words: reactive oxygen species Ⅲ endothelium Ⅲ nitric oxide Ⅲ superoxide dismutase Ⅲ peroxynitrite S uperoxide anion (O 2 Ϫ ) and other reactive oxygen species (ROS) play a major role in vascular biology. In general, relatively low concentrations of ROS are thought to act as mediators or modulators of cell signaling and contribute to other key functions, such as regulation of activity of transcription factors and gene expression. [1][2][3] In contrast, higher levels of ROS contribute to vascular dysfunction and abnormal cell growth including hypertrophy of vascular muscle. Superoxide levels are increased in blood vessels in many pathophysiological conditions including hypertension, atherosclerosis, diabetes, hyperhomocysteinemia, heart failure, sepsis, subarachnoid hemorrhage, and Alzheimer disease, as well as during aging. Since the initial evidence that superoxide or other ROS inactivate nitric oxide (NO) or endothelium-derived relaxing factor (EDRF), 4 many studies have suggested that inactivation of NO by superoxide contributes to vascular dysfunction under pathophysiological conditions. Steady-state levels of superoxide are dependent on both its rate of production as well as activity of the various superoxide dismutases (SODs). The goal of this review is to briefly summarize the role of SODs in relation to vascular biology with an emphasis on endothelium. This summary will mainly focus on highlighting recent work from an emerging field, the functional importance of specific SOD isoforms in vascular protection. Superoxide Dismutases: Basic Characteristics and FunctionsIn mammals, there are 3 isoforms of SOD, 5 and each are products of distinct genes but catalyze the same reaction: As indicated above, SODs dismute superoxide into hydrogen peroxide plus molecular oxygen. There are several functional consequences of this enzymatic activity. First, SODs protect against superoxide-mediated cytotoxicity, such as inactivation of mitochondrial proteins containing ironsulfur (Fe-S) centers (eg, aconitase and fumarase) ( Figure 2). 5 Such interactions are of potential importance, as damage to such complexes results in release of free i...

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…SOD is the primary scavenger of O 2 ·-in endothelial cells, through a reduction of two O 2 ·-molecules resulting in H 2 O 2 and O 2 (Griendling et al 2000a;Salvemini et al 2002). The total percentage of each SOD isoform expressed in different vascular cells was recently reviewed by Faraci et al (Faraci et al 2004). High levels of MnSOD were found in endothelial cells.…”

“…ONOO -is formed through the interaction of NO and O 2 ·- Wattanapitayakul et al 2000;Guzik et al 2002) and O 2 ·-are roughly equivalent (Faraci et al 2004). NO availability is reduced with elevated concentrations of O 2 ·-, through the formation of ONOO -.…”

“…ecSOD also associates with heparan sulfate proteoglycan on the endothelial cell membrane after production by SMC (Faraci et al 2004). SOD is the primary scavenger of O 2 ·-in endothelial cells, through a reduction of two O 2 ·-molecules resulting in H 2 O 2 and O 2 (Griendling et al 2000a;Salvemini et al 2002).…”

Significance of measuring oxidative stress in lifestyle-related diseases from the viewpoint of correlation between d-ROMs and BAP in Japanese subjects

“…[4][5][6][7] On the other hand, as indices of antioxidant potential, intracellular levels of superoxide dismutase and glutathione peroxidase have mainly been measured. [8][9] However, these assay methods are complex and are not suitable for analysis of a large number of subjects. Recently, simpler methods for detecting reactive oxygen species (ROS) using derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were developed, and reports on studies using these methods have been increasing.…”

Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people

“…$ p<0.05 versus 2-h after meal intake. Different letters: the differences between diets are statistically significant (p<0.05) (Faraci and Didion 2004;Mates et al 1999;Rahman et al 2005). Our results showed that the gene expression of the mitochondrial SOD isoform, SOD2, seems to be modulated by dietary fat rather than by the cytoplasmatic isoform SOD1.…”