Abstract
Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). However, how highly diffusible ROS produced from different sources and location can communicate with each other to regulate angiogenesis remains unclear. To detect a localized ROS signal in distinct subcellular compartments in real time in situ, compartment-specific genetically encoded redox-sensitive fluorescence biosensors have been developed. Recently, the intercellular communication, “cross-talk”, between ROS derived from NOX and mitochondria, termed “ROS-induced ROS release”, has been proposed as a mechanism for ROS amplification at distinct subcellular compartments, which are essential for activation of redox signaling. This “ROS-induced ROS release” may represent a feed-forward mechanism of localized ROS production to maintain sustained signaling, which can be targeted under pathological conditions with oxidative stress or enhanced to promote therapeutic angiogenesis. In this review, we summarize the recent knowledge regarding the role of the cross-talk between NOX and mitochondria organizing the sustained ROS signaling involved in VEGF signaling, neovascularization and tissue repair.
Highlights
Angiogenesis is the process of a new blood vessel formation from pre-existing vasculature
This review will summarize the recent knowledge regarding the role of Reactive oxygen species (ROS)-induced ROS organized by the cross-talk between ROS derived from NADPH oxidase (NOX) and mitochondria in driving angiogenesis, in particular, focusing on Vascular endothelial growth factor (VEGF) signaling
ROS at the appropriate level are increased in response to growth factors (e.g.,VEGF), ischemia or wound injury, which function as signaling molecules to promote the angiogenic switch from quiescent endothelial cells (ECs) (Figure 1)
Summary
Angiogenesis is the process of a new blood vessel (capillaries) formation from pre-existing vasculature. Nox or p22phox to produce O2 − in fibroblasts and smooth muscle cells [16]; uncoupled eNOS produces O2 − , instead of NO, to enhance mitochondrial ROS (mitoROS) production [17,18]; NOX-derived ROS increase mitochondrial ROS [13,19]; and mitochondrial ROS stimulate NOX activation [20] This feed-forward ROS-induced ROS release mechanism can be targeted to inhibit pathological angiogenesis associated with oxidative stress or promote ROS-dependent physiological and therapeutic angiogenesis. This review will summarize the recent knowledge regarding the role of ROS-induced ROS organized by the cross-talk between ROS derived from NOX (plasma membrane and cytosol) and mitochondria in driving angiogenesis, in particular, focusing on VEGF signaling Understanding these mechanisms should provide new insights into therapeutic strategies for various angiogenesis-dependent cardiovascular diseases and cancer
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