Erik Ehinger1, Yanal Ghosheh1, Akula Bala Pramod1, Juan Lin2, David B Hanna2, Karin Mueller1, Christopher P Durant1, Livia Baas1, Qibin Qi2, Tao Wang2, Konrad Buscher1, Kathryn Anastos3, Jason M Lazar4,5, Wendy J Mack6, Phyllis C Tien7,8, Mardge H Cohen9, Igho Ofotokun10, Stephen Gange11, Sonya L Heath12, Howard N Hodis13, Russell P Tracy14, Alan L Landay15, Robert C Kaplan2,16, Klaus Ley1,17. 1. Laboratory of Inflammation Biology, La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. 2. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. 3. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. 4. Department of Medicine, State University of New York, Downstate Medical Center, Bronx, NY, USA. 5. Department of Epidemiology & Population Health, State University of New York, Downstate Medical Center, Bronx, NY, USA. 6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 7. Department of Medicine and Medical Service, University of California, San Francisco, San Francisco, CA, USA. 8. Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA. 9. Department of Medicine, John Stroger Hospital and Rush University, Chicago, IL, USA. 10. Department of Medicine, Infectious Disease Division and Grady Health Care System, Emory University School of Medicine, Atlanta, GA, USA. 11. Division of Cardiovascular Medicine, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA. 12. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 13. Departments of Medicine and Preventative Medicine, Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 14. Department of Pathology & Laboratory Medicine and Biochemistry, University of Vermont Larner College of Medicine, Colchester, VT, USA. 15. Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. 16. Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle WA 98109, USA. 17. Department of Bioengineering, University of California San Diego, San Diego, CA, USA.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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