ApoA-I mimetics favorably impact cyclooxygenase 2 and bioactive lipids that may contribute to cardiometabolic syndrome in chronic treated HIV
| Autor: | Scott G. Kitchen, Shubhendu Sen Roy, Victor Grijalva, Jeremy Papesh, David Meriwether, Athanasios Kossyvakis, Rachel Heymans, Theodoros Kelesidis, Valerie Rezek, Arnab Chattopadhyay, M. Sharma, Eleni Ritou, Philip Hamid, Srinu T Reddy, Alan M. Fogelman, M. Daskou, William Mu |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Apolipoprotein B Endocrinology Diabetes and Metabolism Clinical Sciences Inflammation HIV Infections Pharmacology Systemic inflammation Cardiovascular Article Proinflammatory cytokine Cardiometabolic syndrome Mice Endocrinology & Metabolism Endocrinology In vivo Clinical Research Internal medicine medicine Animals Secretion ApoA-I mimetic peptides Metabolic Syndrome biology Apolipoprotein A-I Bioactive lipids business.industry Prevention Chronic treated HIV Atherosclerosis Infectious Diseases Cyclooxygenase 2 5.1 Pharmaceuticals biology.protein Eicosanoids HIV/AIDS lipids (amino acids peptides and proteins) Cyclooxygenase medicine.symptom Development of treatments and therapeutic interventions business Peptides Infection Ex vivo Biotechnology |
| Zdroj: | Metabolism: clinical and experimental |
| Popis: | Objective We investigated whether apolipoprotein A-I (apoA-I) mimetic peptides 4F and 6F can be a novel therapeutic strategy to reduce blood and gut bioactive lipids, proinflammatory effects of endotoxin (LPS) and aberrant activation of cyclooxygenase 2 (COX-2) as instigators of increased risk for cardiometabolic disease in chronic treated HIV. Methods We used two humanized murine models of chronic treated HIV infection (n = 109 mice) and gut explants from HIV infected (n = 10) persons to determine whether Tg6F and 4F attenuate in vivo and ex vivo increased blood and gut bioactive lipids (measured by mass spectrometry) and intestinal protein levels of COX-2 (measured by immunoassays) in chronic treated HIV. Results In these models of HIV, when compared to HIV-1 infected mice on antiretroviral therapy (ART) alone, oral Tg6F in combination with ART attenuated increases in plasma and gut bioactive lipids (and particularly COX lipids) and intestinal COX-2. 4F and Tg6F also reduced ex vivo production of COX-2 protein and associated secretion of bioactive lipids in gut explants from HIV-1 infected persons treated with LPS. Conclusion ApoA-I mimetics favorably impact the proinflammatory effects of LPS, COX-2 and production of bioactive lipids that collectively drive gut and systemic inflammation in chronic treated HIV. Given prior experimental evidence that the proinflammatory effects of LPS, COX-2 and gut dysfunction contribute to cardiometabolic syndrome in chronic HIV, apoA-I mimetic peptides may be a novel therapy to treat cardiometabolic syndrome in chronic HIV. |
| Databáze: | OpenAIRE |
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