Oxidative stress in angiogenesis and vascular disease

Abstract

Despite the damaging effect on tissues at a high concentration, it has been gradually established that oxidative stress plays a positive role during angiogenesis. In adults, physiological or pathological angiogenesis is initiated by tissue demands for oxygen and nutrients, resulting in a hypoxia/reoxygenation cycle, which, in turn promotes the formation of reactive oxygen species (ROS). The ROS can be generated either endogenously, through mitochondrial electron transport chain reactions and nicotinamide adenine dinucleotide phosphate oxidase, or exogenously, resulting from exposure to environmental agents, such as ultraviolet or ionizing radiation. In many conditions, ROS promotes angiogenesis, either directly or via the generation of active oxidation products, including peroxidized lipids. The latter lipid metabolites are generated in excess during atherosclerosis, thereby linking atherogenic processes and pathological angiogenesis. Although the main mechanism of oxidative stress-induced angiogenesis involves hypoxia-inducible factor/vascular endothelial growth factor (VEGF) signaling, recent studies have identified several pathways that are VEGF-independent. This review aims to provide a summary of the past and present views on the role of oxidative stress as a mediator and modulator of angiogenesis, and to highlight newly identified mechanisms.

The mitochondrial dynamics in cancer and immune-surveillance

“…Further, the pro-angiogenesis activity of tumor cells becomes crucial for their survival in a microenvironment progressively more hypoxic, for a continuous supply of nutrients and oxygen [116]. The hypoxic TME triggers, also through oxidative stress −as shown in ovarian and prostate cancers [117][118][119], the tumor production of angiogenetic factors such as vascular-endothelial-growth-factor (VEGF), by upregulating hypoxia-inducible factor-1α (HIF-1α) [120]. Interestingly, HIF-1α is able to limit ROS accumulation in tumor cells, thus promoting cancer progression at later stages, by limiting the production of acetyl-CoA (the key molecule entering the TCA cycle) from glycolysis [121] and fattyacid oxidation [122].…”

Hypoxia, Angiogenesis and Atherogenesis

“…Although ROS have damaging effects on tissues, causing cell death at high concentrations, lesser degrees of oxidative stress may play a positive role during angiogene- sis, or other pathophysiological processes. Angiogenesis induced by oxidative stress involves vascular endothelial growth factor (VEGF) signalling, although VEGF-independent pathways have also been identified [44].…”

LOX-1 is implicated in oxidized low-density lipoprotein-induced oxidative stress of macrophages in atherosclerosis

“…p38 MAPK has been implicated in the development of atherosclerosis via promotion of cholesterol ester accumulation in macrophages and foam cell formation (6). Despite extensive studies on the role of ROS in atherosclerosis (3)(4)(5), relatively little is known about the molecular mechanisms underlying the regulation of ROS production.…”

“…One of the early events of atherogenesis is the formation of foam cells, which are macrophages with ingested oxidized low-density lipoprotein (OxLDL) (2). Compelling evidence indicates that oxidative stress, particularly excessive production of reactive oxygen species (ROS), has a causal role in atherosclerosis (3,4). Lipid oxidation triggered by ROS can amplify foam cell formation through oxLDL formation and uptake.…”