Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury

Abstract

The development of vascular disease has its origins in an initial insult to the vessel wall by biological or mechanical factors. The disruption of homeostatic mechanisms leads to alteration of the original architecture of the vessel and its biological responsiveness, contributing to acute or chronic diseases such as stroke, hypertension, and atherosclerosis. Endothelial dysfunction, macrophage infiltration of the vessel wall, and proliferation and migration of smooth muscle cells all involve different types of reactive oxygen species produced by various vessel wall components. Although basic science and animal research have clearly established the role of reactive oxygen species in the progression of vascular disease, the failure of clinical trials with antioxidant compounds has underscored the need for better antioxidant therapies and a more thorough understanding of the role of reactive oxygen species in cardiovascular physiology and pathology.

Figure 1

ROS production in vascular injury. a.Dihydroethidium (DHE) staining for superoxide of a stage II atherosclerotic lesion with signs of intimal hyperplasia (left) and stage V atherosclerotic where a complex plaque is already present with substantial intimal hyperplasia and partial occlusion of the arterial lumen (right). The red fluorescence shows intense superoxide production in all layers of the arterial wall. L=lumen. (Photograph courtesy of D. Sorescu). b.Superoxide production in rat carotid arteries after balloon injury. The arteries were balloon-injured and stained with dihydroethidium (DHE). Shown are a normal carotid and a carotid harvested 15 days after balloon injury. L=lumen. Modified from (Szocs et al. 2002).

Figure 2

Sources of ROS in vascular cells. All components of the vascular wall produce ROS. Enzymatic sources include NADPH oxidases, lipoxygenases, heme oxygenase, xanthine oxidase, uncoupled eNOS, uncoupled mitochondrial electron transport and myeloperoxidase.

Figure 3

Role of ROS in the response to injury. Reactive oxygen species mediate many of the responses to vascular injury. Both mechanical factors and biological factors produced in response to injury can stimulate the production of reactive oxygen species in macrophages, endothelial cells, smooth muscle cells and adventitia. These ROS then impair vessel tone and promote an inflammatory response, and increase smooth muscle cell migration, proliferation and apoptosis. Figure depicting migration shows VSMCs migrating into a wound area stained with hematoxylin and eosin after stimulation with PDGF. Figure depicting inflammation shows the shoulder region of a plaque stained for macrophages. Adapted from (Sorescu et al. 2002) Figure depicting apoptosis is a GFP-transfected cell stained with phalloidin. (Courtesy of Alicia Lyle)