Overexpression Of Mnsod Provides Protection Against Nrti- Induced Endothelial Dysfunction In A Drug-Dependent Manner

Nucleoside reverse transcriptase inhibitors (NRTI) currently used in HIV therapy have been linked to cardiovascular toxicity. Our prior studies have demonstrated alterations in mitochondrial function and upregulation of mitophagy in endothelial cells after acute treatment, with parameters returning to normal by 24 h. Treatment with coenzyme Q10 prevented this toxicity, suggesting a role for antioxidant supplementation. The current study utilized mice overexpressing MnSOD to determine the protective effects of this mitochondrial antioxidant enzyme. Measurements of plasma vasodilators, vasoconstrictors, and markers of oxidative stress, along with vessel reactivity experiments were used to assess protective effects. Results indicate that although wild‐type mice treated with either AZT or 3TC exhibited reduced vessel reactivity, overexpression of MnSOD only attenuated 3TC‐induced effects. Plasma markers of vascular function either correlated with this finding, or demonstrated MnSOD protection for both NRTI. These findings suggest differential mechanisms of toxicity of the 2 drugs. Supported by R01‐HL08242–0251. Grant Funding Source : R01‐HL08242–0251