The role of HIV Tat protein in HIV-related cardiovascular diseases

Jiang, Yanan; Chai, Lu; Fasae, Moyondafoluwa Blessing; Bai, Yunlong

doi:10.1186/s12967-018-1500-0

Cited by 22 publications

(16 citation statements)

References 71 publications

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“…The regulatory Tat protein not only facilitates the transcription of HIV, but it is also implicated in the pathogenesis of endothelial dysfunction and atherosclerosis-associated CV complications in PLWH [51]. In contrast to our results supporting indirect effects of Tat on endothelial function mediated via leptin reduction, others have reported that HIV protein Tat stimulates oxidative stress by increasing ROS production and decreasing antioxidant capacity [52][53][54][55].…”

Section: Discussioncontrasting

confidence: 81%

Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice

Kovács

Bruder‐Nascimento

Greene

et al. 2021

IJMS

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People living with human immunodeficiency virus (HIV) (PLWH) have increased risk for atherosclerosis-related cardiovascular disease (CVD), the main cause of death in this population. Notwithstanding, the mechanisms of HIV-associated vascular pathogenesis are not fully elucidated. Therefore, we sought to determine whether HIV-regulatory protein Tat mediates HIV-induced endothelial dysfunction via NADPH oxidase 1 (Nox1)-dependent mechanisms. Body weight, fat mass, leptin levels, expression of reactive oxygen species (ROS)-producing enzymes and vascular function were assessed in C57BL/6 male mice treated with Tat for 3 days and 4 weeks. Aortic rings and human endothelial cells were also treated with Tat for 2–24 h in ex vivo and in vitro settings. Chronic (4 weeks) but not acute (3 days and 2–24 h) treatment with Tat decreased body weight, fat mass, and leptin levels and increased the expression of Nox1 and its coactivator NADPH oxidase Activator 1 (NoxA1). This was associated with impaired endothelium-dependent vasorelaxation. Importantly, specific inhibition of Nox1 with GKT771 and chronic leptin infusion restored endothelial function in Tat-treated mice. These data rule out direct effects of HIV-Tat on endothelial function and imply the contribution of reductions in adipose mass and leptin production which likely explain upregulated expression of Nox1 and NoxA1. The Nox1 and leptin system may provide potential targets to improve vascular function in HIV infection-associated CVD.

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Section: Discussioncontrasting

confidence: 81%

Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice

Kovács

Bruder‐Nascimento

Greene

et al. 2021

IJMS

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“…Changes in the adaptive immune system and persistent inflammation leading to severe ventricular electrophysiological remodeling could be the possible mechanisms. Indeed, experimental evidence, especially transgenic mouse models, provide a view of the pathophysiological mechanisms of HIV-related arrhythmia and strongly support the role for inflammation and pro-inflammatory cytokines (tumor necrosis factor-alpha [TNFα] and interleukin [IL]-1β) on cardiac potassium and calcium ion channels and associated pathologic electrical remodeling [18][19][20][21]. IL-1β decreases the calcium currents, whereas TNFα reduces potassium and sodium currents without affecting calcium currents.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Dispersion of Ventricular Repolarization as a Risk Factor in Patients with Human Immunodeficiency Virus: Tp-e Interval, Tp-e/QTc Ratio

et al. 2020

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Highlights of the Study • The cTp-e interval and the Tp-e/QT and Tp-e/corrected QTC (QTc) ratios were found to be prolonged in Human Immunodeficiency Virus (HIV)-infected patients as compared to healthy subjects. • There was an inverse correlation between cTp-e interval, Tp-e/QTc ratio, and CD4 count, and a correlation between cTp-e interval, Tp-e/QTc ratio, and high-sensitivity C-reactive protein (hsCRP). • Prolonged cTp-e interval, Tp-e/QTc ratio, and abnormal dispersion of ventricular repolarization may suggest an increased risk for ventricular arrhythmias and mortality in HIV-infected individuals.

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“…Urbinati and co-workers in 2012 found that immobilized Tat induces actin cytoskeleton organization, formation of a v b 3 integrin(+)focal adhesion plaques, and recruitment of vascular endothelial growth factor receptor-2 (VEGFR2) in the ventral plasma membrane of adherent endothelial cells (96). Tat binding to the endothelial cells may also directly contribute to atherosclerosis and cardiovascular disease in patients with HIV (97).…”

Section: Endothelial Cells and Hiv-1 Protein Interactionsmentioning

confidence: 99%

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Pretorius

2021

Front. Immunol.

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The immune and inflammatory responses of platelets to human immunodeficiency virus 1 (HIV-1) and its envelope proteins are of great significance to both the treatment of the infection, and to the comorbidities related to systemic inflammation. Platelets can interact with the HIV-1 virus itself, or with viral membrane proteins, or with dysregulated inflammatory molecules in circulation, ensuing from HIV-1 infection. Platelets can facilitate the inhibition of HIV-1 infection via endogenously-produced inhibitors of HIV-1 replication, or the virus can temporarily hide from the immune system inside platelets, whereby platelets act as HIV-1 reservoirs. Platelets are therefore both guardians of the host defence system, and transient reservoirs of the virus. Such reservoirs may be of particular significance during combination antiretroviral therapy (cART) interruption, as it may drive viral persistence, and result in significant implications for treatment. Both HIV-1 envelope proteins and circulating inflammatory molecules can also initiate platelet complex formation with immune cells and erythrocytes. Complex formation cause platelet hypercoagulation and may lead to an increased thrombotic risk. Ultimately, HIV-1 infection can initiate platelet depletion and thrombocytopenia. Because of their relatively short lifespan, platelets are important signalling entities, and could be targeted more directly during HIV-1 infection and cART.

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The role of HIV Tat protein in HIV-related cardiovascular diseases

Cited by 22 publications

References 71 publications

Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice

Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice

Abnormal Dispersion of Ventricular Repolarization as a Risk Factor in Patients with Human Immunodeficiency Virus: Tp-e Interval, Tp-e/QTc Ratio

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

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