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AIDS. 2018 Apr 24;32(7):867-876. doi: 10.1097/QAD.0000000000001762.

Novel mediators of statin effects on plaque in HIV: a proteomics approach.

Author information

1
Inova Heart and Vascular Institute, Falls Church, Virginia.
2
Program in Nutritional Metabolism, MGH and Harvard Medical School, Boston.
3
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
4
Olink Proteomics, Watertown.
5
MGH Biostatistics Center, MGH and Harvard Medical School, Boston, Massachusetts.

Abstract

OBJECTIVE:

HIV patients have increased atherosclerotic coronary vascular disease (ASCVD), thought to be mediated through inflammatory mechanisms. We hypothesized that among asymptomatic HIV-infected patients with subclinical coronary plaque, statin therapy would modulate unique inflammatory and cardiovascular proteins in relation to change in subclinical coronary plaque volume. We tested this hypothesis using a novel proteomics approach.

DESIGN:

Forty HIV-infected participants were randomized to atorvastatin (40 mg/day) versus placebo, and underwent computed tomography coronary angiography to quantify plaque volume at baseline and 1 year.

METHODS:

We used Olink Cardiovascular III and Cardiometabolic panels based on dual antibody epitope recognition with linked DNA amplification to compare change over time in 184 proteins in treatment versus placebo and in relation to change in coronary plaque volume.

RESULTS:

Six proteins (TFPI, CCL24, NT-Pro BNP, MBL2, LTBR, PCOLCE) changed significantly in the atorvastatin versus placebo group, many in innate immune and other novel inflammatory pathways. Twenty-six proteins changed significantly in relationship to total coronary plaque volume over 1 year. Notably, many of these proteins changed only weakly in relationship to change in low-density lipoprotein (LDL). Overlapping these two broad discovery approaches, proteins involved in myocardial fibrosis/collagen formation and monocyte chemoattraction changed with statin treatment, in relationship to plaque volume, but not LDL.

CONCLUSION:

This proof-of-concept study employing a proteomic discovery platform offers insight into statin effects on novel immune pathways relevant to ASCVD progression in HIV. Novel biomarker discovery may enhance precision medicine strategies to estimate the efficacy of targeted therapies to reduce ASCVD progression and events in HIV.

PMID:
29369166
PMCID:
PMC5869115
[Available on 2019-04-24]
DOI:
10.1097/QAD.0000000000001762

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