Proteomic Profile After Intervention With Eplerenone Among Persons With HIV

Area of Science:

• Cardiovascular Science
• HIV Medicine
• Proteomics

Background:

• Individuals with well-managed human immunodeficiency virus (HIV) exhibit elevated arterial inflammation, increasing atherosclerotic disease risk.
• Previous studies demonstrated eplerenone's efficacy in reducing arterial inflammation in people with HIV, measured by cardiac ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (TBR).
• The precise mechanisms underlying eplerenone's beneficial effects on arterial inflammation remain to be elucidated.

Purpose of the Study:

• To identify a proteomics signature associated with eplerenone treatment in people with HIV.
• To elucidate potential mechanisms by which eplerenone reduces arterial inflammation and cardiovascular disease risk.
• To explore the relationship between specific protein expression changes and arterial inflammation reduction.

Main Methods:

• A targeted proteomics approach was employed using samples from the MIRABELLA HIV trial (NCT02740179).
• 276 cardiovascular and cardiometabolic proteins were analyzed using Olink technology.
• Proteomic data was correlated with changes in arterial inflammation (TBR) and treatment groups (eplerenone vs. placebo).

Main Results:

• Eleven proteins showed differential expression between eplerenone and placebo groups.
• Eight proteins, including CDH1, FGF-21, and Gal-4, decreased with eplerenone treatment.
• Changes in TBR correlated significantly with altered expression of CDH1, FGF-21, and Gal-4.

Conclusions:

• Eplerenone treatment in people with HIV is associated with decreased expression of CDH1, FGF-21, and Gal-4.
• These proteins are implicated in inflammation, vascular dysfunction, and metabolic dysregulation.
• The observed protein changes provide mechanistic insights into eplerenone's potential to mitigate cardiovascular disease in HIV-infected individuals.