ABSTRACT
The key role of the vasculature is to provide oxygen for the metabolic demand of the tissues throughout the periphery of an organism. Although this seems like a straightforward task, oxygen itself is a highly reactive molecule that when combined with other substrates can have a multitude of effects, both deleterious and beneŸcial. For example, reactive oxygen species (ROS) can include hydroxyl radical and superoxide anion radical, which are both known for their deleterious effects on tissues. Conversely, nitric oxide (NO) is the most important ROS in the vasculature where it is well known for its beneŸcial effects. One of the deŸning features for each of these ROS molecules is the presence of a free radical, an unpaired electron in the
9.1 Introduction .................................................................................................. 157 9.1.1 Vascular Structure ............................................................................ 158 9.1.2 Vascular Cxs ..................................................................................... 158 9.1.3 Oxidative Stress and Reactive Oxygen Species ................................ 159 9.1.4 Posttranslational ModiŸcations: Phosphorylation ............................ 161 9.1.5 Posttranslational ModiŸcations: Nitrosylation ................................. 163
9.2 Metabolic Syndrome ..................................................................................... 165 9.2.1 Atherosclerosis .................................................................................. 165 9.2.2 Angioplasty and Restenosis .............................................................. 168 9.2.3 Cx Genetics in Oxidative Stress ....................................................... 169 9.2.4 Type 2 Diabetes and Obesity ............................................................ 170 9.2.5 InŽammation .................................................................................... 172
9.3 Hypertension ................................................................................................. 174 9.3.1 Pulmonary Hypertension .................................................................. 174 9.3.2 Renal Hypertension .......................................................................... 175
9.4 Angiogenesis in Cancer ................................................................................ 177 9.5 Future Directions .......................................................................................... 179 References .............................................................................................................. 180
outer orbital, which can cause the molecule to be highly reactive. Although most of the ROS originate from the superoxide anion radical that are mostly produced by mitochondria or NADPH oxidase (Demaurex and Scorrano, 2009), the endothelial cells (ECs) lining the inside of the blood vessels produce vast amount of NO via the enzyme endothelial NO synthase (eNOS, NOS3). In the vasculature, NO is quite beneŸcial by providing a relaxation signal to the vascular smooth muscle cells (VSMCs) to dilate, or provide a measure of inŽammatory inhibition by preventing the binding of leukocytes to the endothelium. However, other ROS molecules, especially superoxide anion can be produced during pathological events in the vasculature (e.g., ischemic conditions) and have deleterious effects (for review, see Wolin, 2009). Although it has been hypothesized that ROS, and especially hydrophilic ROS such as superoxide anion and hydroxyl radical, could pass through gap junctions (Tang and Vanhoutte, 2008; Billaud et al., 2009), ROS molecules provide a different method of communication than gap junctions, which allow for direct intercellular transfer of molecules. This review focuses on the published observations and possible mechanisms that allow oxidative events by ROS to alter both connexin (Cx) expression and function, which by extension, would alter (or enhance) the status of the vasculature.
