Metabolic and Redox Pathway Dysregulation in HIV-Associated Coronary Endothelial Dysfunction
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
People with HIV (PWH), even with sustained viral suppression on antiretroviral therapy (ART), remain at increased risk for cardiovascular disease. Coronary endothelial dysfunction, a sensitive marker of early vascular injury and a potential target for intervention is common in this population, but its biological basis remains unknown.
Methods
We performed a cross-sectional study combining in vivo coronary MRI and high-throughput serum proteomics to investigate mechanisms of coronary endothelial dysfunction in treated HIV. Forty-five virally suppressed PWH and twenty-nine age- and sex-matched healthy controls underwent coronary MRI during isometric handgrip exercise to quantify coronary endothelial function, defined as the percentage change in coronary cross-sectional area (%CSA) from rest to stress. An increase in coronary CSA <2% indicated endothelial dysfunction. Parallel serum proteomic profiling was performed using the SomaScan 7K platform, and differential protein expression between groups was analyzed using linear modeling (LIMMA).
Results
Coronary endothelial dysfunction was more prevalent in PWH with suppressed viral load compared to controls (67% vs 10%, p<0.001). Pathway analysis of differentially expressed proteins between participants with and without endothelial dysfunction highlighted significant dysregulation of glutathione dependent detoxification, oxidative metabolism and fatty acid β-oxidation pathways in individuals with endothelial dysfunction (adjusted p value <0.05).
Conclusions
Endothelial dysfunction in PWH on ART is associated with metabolic and redox imbalance. These findings highlight glutathione and fatty acid oxidation related pathways as potential therapeutic targets for reducing cardiovascular risk in this patient population.
