Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation

Pablo, Carmen de; Orden, Samuel; Apostolova, Nadezda; Blanquer, Amando; Esplugues, Juan V.; Álvarez, Ángeles

doi:10.1097/qad.0b013e32833a2b02

Cited by 42 publications

(37 citation statements)

References 35 publications

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“…Initiation of an ABC-containing ART was associated with smaller reductions in inflammatory markers than ART not containing ABC [90], although this is not a consistent finding across studies [91]. In vitro, ABC increases the adhesion of leukocytes to endothelial cells, through leucocyte activation [92] and also increased platelet reactivity through inhibition of soluble guanylyl cyclase [93]. These findings have also been confirmed in vivo.…”

Section: No Abacavirsupporting

confidence: 59%

Dyslipidemia, Atherosclerosis and Cardiovascular Disease: An Increasingly Important Triad in an Aging Population Living with HIV

2013

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As a result of major advances in the management of HIV over the last two decades, patients living with HIV are now encountering comorbidities commonly associated with aging. Cardiovascular disease is the leading cause of death worldwide. As the population living with HIV ages, understanding cardiovascular disease in the setting of HIV is of increasing importance. This review examines the complex interplay between cardiovascular disease, HIV infection and the drugs used to treat it, with particular emphasis on the contribution of dyslipidemia.

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Section: No Abacavirsupporting

confidence: 59%

Dyslipidemia, Atherosclerosis and Cardiovascular Disease: An Increasingly Important Triad in an Aging Population Living with HIV

2013

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“…Accumulation of these cells in the vessel wall is a hallmark of atherosclerosis and acute coronary syndrome, and is mediated by the interaction between adhesion molecules on endothelial and circulating cells. In an experimental system, Pablo et al recently demonstrated that ABC but not AZT or 3TC induced significant and dose-dependent increases in rolling flux and adhesion in the leukocyte-endothelium interaction [25]; these effects were blocked by antibodies against ICAM-1 or Mac-1. Furthermore, treatment of neutrophils and monocytes with ABC increased the expression of Mac-1, whereas no increases in ICAM-1, VCAM-1, or E-selectin were seen following the treatment of endothelial cells [25].…”

Section: Discussionmentioning

confidence: 99%

“…In an experimental system, Pablo et al recently demonstrated that ABC but not AZT or 3TC induced significant and dose-dependent increases in rolling flux and adhesion in the leukocyte-endothelium interaction [25]; these effects were blocked by antibodies against ICAM-1 or Mac-1. Furthermore, treatment of neutrophils and monocytes with ABC increased the expression of Mac-1, whereas no increases in ICAM-1, VCAM-1, or E-selectin were seen following the treatment of endothelial cells [25]. Altogether, these results suggest that ABC treatment could be linked to increased expression of Mac-1 rather than endothelial adhesion molecules, which would explain the paucity of positive results in studies of the latter.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cardiovascular biomarkers In HIV-infected patients switching to abacavir or tenofovir based therapy

et al. 2011

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BackgroundOur objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk.MethodsIn an open-label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin, and myeloperoxidase (MPO) at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test.ResultsOf 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P = 0.004) and sVCAM-1 (P = 0.041) increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL) increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio.ConclusionIn patients randomized to abacavir-based HIV-treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain.Trial RegestrationClinicaltrials.gov identifier: NCT00647244.

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“…ABC and ddI have been widely associated with a higher risk of cardiovascular events in HIV-infected patients [77,78], which has been confirmed by several in vitro studies [79]. However, the implication of mitochondrial dysfunction and oxidative stress in the induction of these effects is still unclear.…”

Section: Nucleoside Reverse Transcriptase Inhibitors (Nrti)mentioning

confidence: 95%

Oxidative Stress and Mitochondrial Impairment After Treatment with Anti-HIV Drugs: Clinical Implications

Blas‐García

Apostolova²,

Esplugues³

2011

CPD

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Thirty years after the discovery of HIV infection, there are numerous antiretroviral drugs that control the disease when administered in a potent combination referred to as Highly Active Antiretroviral Therapy (HAART). This therapy reduces the viral load and improves immune system reconstitution, leading to a significant reduction of HIV-related morbidity and mortality. However, HAART does not completely eliminate HIV, so treatment must continue throughout the patient's life. Prolonged use of HAART has been related to long-term adverse events that can compromise patient health. These deleterious effects have been reported for the majority of antiretroviral drugs and are the most common causes for therapy discontinuation. In most of these adverse events, such as diabetes, cardiovascular diseases, neurological disorders and metabolic alterations, oxidative stress and mitochondrial impairment play important roles. This review covers the implication of antiretroviral drugs in the overproduction of reactive oxygen species and the reduction of antioxidant defences, and in the consequent mitochondrial dysfunction, focusing on the molecular mechanisms involved and the clinical implications for HIV-infected patients.

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Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation

Cited by 42 publications

References 35 publications

Dyslipidemia, Atherosclerosis and Cardiovascular Disease: An Increasingly Important Triad in an Aging Population Living with HIV

Dyslipidemia, Atherosclerosis and Cardiovascular Disease: An Increasingly Important Triad in an Aging Population Living with HIV

Evaluation of cardiovascular biomarkers In HIV-infected patients switching to abacavir or tenofovir based therapy

Oxidative Stress and Mitochondrial Impairment After Treatment with Anti-HIV Drugs: Clinical Implications

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