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

Author:

Ehinger Erik1ORCID,Ghosheh Yanal1ORCID,Pramod Akula Bala1,Lin Juan2,Hanna David B2,Mueller Karin1,Durant Christopher P1ORCID,Baas Livia1,Qi Qibin2,Wang Tao2ORCID,Buscher Konrad1,Anastos Kathryn3,Lazar Jason M45,Mack Wendy J6,Tien Phyllis C78,Cohen Mardge H9ORCID,Ofotokun Igho10,Gange Stephen11ORCID,Heath Sonya L12,Hodis Howard N13,Tracy Russell P14,Landay Alan L15,Kaplan Robert C216,Ley Klaus117ORCID

Affiliation:

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

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.

Funder

National Institute of General Medical Sciences

Research Scientist Development Award

National Heart, Lung, and Blood Institute

NIH grants

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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