| Title: |
ApoA-I mimetics attenuate macrophage activation in chronic treated HIV |
| Authors: |
Mu, William; Sharma, Madhav; Heymans, Rachel; Ritou, Eleni; Rezek, Valerie; Hamid, Philip; Kossyvakis, Athanasios; Sen Roy, Shubhendu; Grijalva, Victor; Chattopadhyay, Arnab; Papesh, Jeremy; Meriwether, David; Kitchen, Scott G; Fogelman, Alan M; Reddy, Srinivasa T; Kelesidis, Theodoros |
| Source: |
AIDS, vol 35, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3207 Medical Microbiology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3204 Immunology (for-2020); Infectious Diseases (rcdc); HIV/AIDS (rcdc); Clinical Research (rcdc); Biotechnology (rcdc); 5.1 Pharmaceuticals (hrcs-rac); 2.1 Biological and endogenous factors (hrcs-rac); Infection (hrcs-hc); Animals (mesh); Apolipoprotein A-I (mesh); Biomarkers (mesh); HIV Infections (mesh); Lipopolysaccharide Receptors (mesh); Macrophage Activation (mesh); Mice (mesh); apolipoprotein A-I mimetic peptides; chronic treated HIV; immune activation; 06 Biological Sciences (for); 11 Medical and Health Sciences (for); 17 Psychology and Cognitive Sciences (for); Virology (science-metrix); 42 Health sciences (for-2020) |
| Subject Geographic: |
543 - 553 |
| Description: |
OBJECTIVES: Despite antiretroviral therapy (ART), there is an unmet need for therapies to mitigate immune activation in HIV infection. The goal of this study is to determine whether the apoA-I mimetics 6F and 4F attenuate macrophage activation in chronic HIV. DESIGN: Preclinical assessment of the in-vivo impact of Tg6F and the ex-vivo impact of apoA-I mimetics on biomarkers of immune activation and gut barrier dysfunction in treated HIV. METHODS: We used two humanized murine models of HIV infection to determine the impact of oral Tg6F with ART (HIV+ART+Tg6F+) on innate immune activation (plasma human sCD14, sCD163) and gut barrier dysfunction [murine I-FABP, endotoxin (LPS), LPS-binding protein (LBP), murine sCD14]. We also used gut explants from 10 uninfected and 10 HIV-infected men on potent ART and no morbidity, to determine the impact of ex-vivo treatment with 4F for 72 h on secretion of sCD14, sCD163, and I-FABP from gut explants. RESULTS: When compared with mice treated with ART alone (HIV+ART+), HIV+ART+Tg6F+ mice attenuated macrophage activation (h-sCD14, h-sCD163), gut barrier dysfunction (m-IFABP, LPS, LBP, and m-sCD14), plasma and gut tissue oxidized lipoproteins. The results were consistent with independent mouse models and ART regimens. Both 4F and 6F attenuated shedding of I-FABP and sCD14 from gut explants from HIV-infected and uninfected participants. CONCLUSION: Given that gut barrier dysfunction and macrophage activation are contributors to comorbidities like cardiovascular disease in HIV, apoA-I mimetics should be tested as therapy for morbidity in chronic treated HIV. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt6cn9w57h; https://escholarship.org/uc/item/6cn9w57h; https://escholarship.org/content/qt6cn9w57h/qt6cn9w57h.pdf |
| DOI: |
10.1097/qad.0000000000002785 |
| Availability: |
https://escholarship.org/uc/item/6cn9w57h; https://escholarship.org/content/qt6cn9w57h/qt6cn9w57h.pdf; https://doi.org/10.1097/qad.0000000000002785 |
| Rights: |
public |
| Accession Number: |
edsbas.42E328BC |
| Database: |
BASE |