👤 Allie R Walpert

Persons with human immunodeficiency virus (HIV) well-treated on antiretrovirals have increased arterial inflammation, which can lead to development of atherosclerotic disease. We have previously shown that treatment with eplerenone can significantly reduce arterial inflammation, as measured by target-to-background ratio (TBR) on cardiac We performed a targeted discovery-based approach to identify a proteomics signature associated with eplerenone treatment that may provide a plausible mechanism for the reduction in arterial inflammation. In an exploratory study, we leveraged analyzable samples from participants who completed the 12-month, placebo-controlled, randomized controlled trial MIRABELLA HIV to evaluate 276 proteins (Olink Target 96 Cardiometabolic, Cardiovascular II, Cardiovascular III), with relevance to cardiovascular and cardiometabolic disease. We identified 11 proteins that differed in expression between treatment groups. Eight proteins (CDH1, CES1, ADM, IL-4RA, FGF-21, FS, FABP2, Gal-4) decreased and 2 proteins increased (CSTB, MPO) in expression with eplerenone compared to placebo. An increase in expression of IL-27 was prevented among eplerenone-treated versus placebo-treated groups. Changes in TBR of the most diseased segment of the index vessel correlated with changes in 3 of these proteins: CDH1 (ρ = 0.53, Through this proteomics approach, we discovered that 3 key proteins, CDH1, FGF-21, and Gal-4, are decreased in parallel with reductions in arterial inflammation after treatment with eplerenone. Eplerenone-induced reductions in these proteins, known to be related to inflammation, epithelial barrier disruption, vascular dysfunction, and metabolic dysregulation, provide mechanistic insight into pathways by which eplerenone may improve cardiovascular disease in HIV. NCT02740179. Show less