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 Anne Lydia Mueller, Christopher P. Durant, Livia Baas, Qibin Qi, Tao Wang, Konrad Buscher, Kathryn Anastos, Jason Lazar, Wendy J. Mack, Phyllis C. Tien, Mardge H. Cohen, Igho Ofotokun, Stephen J. Gange, Sonya L. Heath, Howard N. Hodis, Russell P. Tracy, Alan Landay, Robert C. Kaplan, Klaus Ley
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.