Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies. Biomolecules 2022 Jun 13;12(6)
Date
06/25/2022Pubmed ID
35740948Pubmed Central ID
PMC9221095DOI
10.3390/biom12060823Scopus ID
2-s2.0-85131782032 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Reactive oxygen species (ROS) can be beneficial or harmful in health and disease. While low levels of ROS serve as signaling molecules to regulate vascular tone and the growth and proliferation of endothelial cells, elevated levels of ROS contribute to numerous pathologies, such as endothelial dysfunctions, colon cancer, and fibrosis. ROS and their cellular sources have been extensively studied as potential targets for clinical intervention. Whereas various ROS sources are important for different pathologies, four NADPH oxidases (NOX1, NOX2, NOX4, and NOX5) play a prominent role in homeostasis and disease. NOX1-generated ROS have been implicated in hypertension, suggesting that inhibition of NOX1 may be a promising therapeutic approach. NOX2 and NOX4 oxidases are of specific interest due to their role in producing extra- and intracellular hydrogen peroxide (H2O2). NOX4-released hydrogen peroxide activates NOX2, which in turn stimulates the release of mitochondrial ROS resulting in ROS-induced ROS release (RIRR) signaling. Increased ROS production from NOX5 contributes to atherosclerosis. This review aims to summarize recent findings on NOX enzymes and clinical trials inhibiting NADPH oxidases to target pathologies including diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).
Author List
Sylvester AL, Zhang DX, Ran S, Zinkevich NSAuthors
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of WisconsinNatalya S. Zinkevich PhD Research Scientist I in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Endothelial CellsHumans
Hydrogen Peroxide
Hypertension
NADPH Oxidases
Reactive Oxygen Species
