Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV

Erik Ehinger, Yanal Ghosheh, Akula Bala Pramod, Juan Lin, David B. Hanna, Karin Mueller, Christopher P. Durant, Livia Baas, Qibin Qi, Tao Wang, Konrad Buscher, Kathryn Anastos, Jason M. Lazar, Wendy J. Mack, Phyllis C. Tien, Mardge H. Cohen, Igho Ofotokun, Stephen Gange, Sonya L. Heath, Howard N. HodisRussell P. Tracy, Alan L. Landay, Robert C. Kaplan, Klaus Ley

Research output: Contribution to journalArticlepeer-review

Abstract

AIMS: During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability. METHODS AND RESULTS: Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women's Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women's Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV-sCVD-) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production. CONCLUSION: Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.

Original languageEnglish (US)
Pages (from-to)1166-1177
Number of pages12
JournalCardiovascular research
Volume117
Issue number4
DOIs
StatePublished - Mar 21 2021

Keywords

  • Antiretroviral therapy
  • Cardiovascular disease
  • Gene signature
  • NGS
  • Statins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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