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NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration
Juliano V Alves1, Rafael M da Costa1,2,3,4,5, Wanessa M C Awata1
1Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Summary
High testosterone levels increase cardiovascular risk by generating reactive oxygen species (ROS). This study reveals that NOX4 acts as a protective enzyme, counterbalancing testosterone
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Oxidative Stress Research
Background:
- High testosterone levels are linked to cardiovascular disease risk via reactive oxygen species (ROS) production.
- NADPH oxidases (NOX) are key ROS sources in cardiovascular pathologies.
- The role of NOX4, a specific ROS-producing enzyme, in testosterone-induced endothelial injury is unclear.
Purpose of the Study:
- To investigate whether supraphysiological testosterone levels induce endothelial NOX4 expression to mitigate endothelial injury.
- To elucidate the role of NOX4 in mediating the cardiovascular effects of high testosterone.
Main Methods:
- Human endothelial cells (HMECs, HUVECs) were treated with testosterone (Testo) and NOX4 inhibitors or siRNA.
- In vivo studies involved testosterone administration in male mice to assess endothelial function.
- Measurements included ROS production, nitric oxide (NO) levels, and endothelial cell migration.
Main Results:
- Testosterone increased NOX4 expression and activity in endothelial cells.
- Testosterone-induced ROS production was modulated by NOX1 and NOX4 inhibition.
- Testosterone impaired endothelial function and cell migration, effects exacerbated by NOX4 inhibition.
Conclusions:
- Supraphysiological testosterone levels upregulate endothelial NOX4.
- NOX4 acts as a compensatory protective mechanism against testosterone-induced endothelial dysfunction.
- NOX4's role in hydrogen peroxide formation is crucial in counterbalancing testosterone's detrimental vascular effects.
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