ArticleThe Journal of clinical investigation2003
HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Pooled it
- Prevention of atherosclerosis in patients living with HIV.Vascular health and risk management · 2009Trial
- Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1.PLoS medicine · 2004Trial
- The Role of Nutrition in HIV-Associated Neurocognitive Disorders: Mechanisms, Risks, and Interventions.Life (Basel, Switzerland) · 2025Review
- Intersecting epidemics: immune dysregulation associated with HIV and tuberculosis syndemic contribute to increased risk of hypertensive disease in Sub-Saharan Africa.Frontiers in cardiovascular medicine · 2025Review
- An adverse outcome pathway for cigarette smoke-mediated oxidative stress in plaque formation.Frontiers in toxicology · 2025Review
- Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease.Circulation research · 2024Review
- Article
- Coronary artery disease in patients with human immunodeficiency virus infection.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2021Review
- The Dual Role of Echocardiography in the Diagnosis of Acute Cardiac Complications and Treatment Monitoring for Coronavirus Disease 2019 (COVID-19).Frontiers in cardiovascular medicine · 2020Article
- Could FDG-PET imaging play a role in the detection of progressing atherosclerosis in HIV-infected patients?Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2019Article
- Atherosclerosis in subjects newly diagnosed with human immunodeficiency virus infection.Bioscience reports · 2018Observational
- Review
- HIV as a Cause of Immune Activation and Immunosenescence.Mediators of inflammation · 2017Review
- Metabolic and Cardiovascular Complications in HIV/HCV-Co-infected Patients.Current HIV/AIDS reports · 2016Review
- Inflammation, immune activation, and cardiovascular disease in HIV.AIDS (London, England) · 2016 · on this mapReview
- HIV, highly active antiretroviral therapy and the heart: a cellular to epidemiological review.HIV medicine · 2016Review
- Incidence and predictors of hypertension in adults with HIV-initiating antiretroviral therapy in south-western Uganda.Journal of hypertension · 2015Article
- Monocyte activation from interferon-α in HIV infection increases acetylated LDL uptake and ROS production.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Article
- HIV-1 Nef impairs key functional activities in human macrophages through CD36 downregulation.PloS one · 2014Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor-dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor-induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and cholesteryl ester accumulation independent of dyslipidemia. Studies with LDL receptor null mice demonstrated that low doses of protease inhibitors induce an increase in the level of CD36 and cholesteryl ester in peritoneal macrophages and the development of atherosclerosis without altering plasma lipids. Furthermore, the lack of CD36 protected the animals from protease inhibitor-induced atherosclerosis. Finally, ritonavir increased PPAR-gamma and CD36 mRNA levels in a PKC- and PPAR-gamma-dependent manner. We conclude that protease inhibitors contribute to the formation of atherosclerosis by promoting the upregulation of CD36 and the subsequent accumulation of sterol in macrophages.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.