Plasma homocysteine levels in HIV-infected men with and without lipodystrophy

Deminice, Rafael; Vassimon, Helena Siqueira; Machado, Alcyone Artioli; Paula, Francisco José Albuquerque de; Monteiro, Jacqueline Pontes; Jordão, Alceu Afonso

doi:10.1016/j.nut.2013.04.017

Cited by 9 publications

(12 citation statements)

References 34 publications

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“…However, discontinuation of therapy rapidly increases the virus burden (3,4). For reasons not well understood, patients under highly active antiretroviral therapy frequently develop various metabolic disorders and also HIV-associated neurocognitive disorders (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Sampey

Saifuddin

Schwab

et al. 2016

Journal of Biological Chemistry

178

273

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HIV-1 infection results in a chronic illness because longterm highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/l were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-␤, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5 and 3 stems (TAR microRNAs) bound best to TLR7 and -8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF-B pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART.

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mentioning

confidence: 99%

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Sampey

Saifuddin

Schwab

et al. 2016

Journal of Biological Chemistry

178

273

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“…Nine of the 16 studies selected were excluded from outcome 2 because of the absence of an HIV-infected non-ART group [29,[30][31][32][33][36][37][38][39] (Figure 1). Table 2 describes the characteristics of the 7 studies included in outcome 2.…”

Section: Outcomementioning

confidence: 99%

“…Nine of the 12 studies reported that the mean Hcy concentration was greater in HIV-infected individuals compared to controls. Only five [33,34,36,38,39] and four [33,36,38,39] of the included studies described quantitative folate and vitamin B12 data, respectively (Table 1). A meta-analysis performed on outcome 1 indicated that the plasma Hcy levels in HIV-infected patients were 2.05 µmol/L higher than the plasma Hcy levels in uninfected controls (95%CI: 0.13-4.01, P < 0.01; [30] Norway 15/21 CS 9.2 ± 7.3 9.0 ± 5.0 ---Naisbitt et al [31] England 33/33 CS 11.9 ± 4.7 14.5 ± 5.6 ---Bernasconi et al [32] Swaziland 80/73 COS 7.6 ± 3.6 8.…”

Section: Outcomementioning

confidence: 99%

“…A meta-analysis performed on outcome 1 indicated that the plasma Hcy levels in HIV-infected patients were 2.05 µmol/L higher than the plasma Hcy levels in uninfected controls (95%CI: 0.13-4.01, P < 0.01; [30] Norway 15/21 CS 9.2 ± 7.3 9.0 ± 5.0 ---Naisbitt et al [31] England 33/33 CS 11.9 ± 4.7 14.5 ± 5.6 ---Bernasconi et al [32] Swaziland 80/73 COS 7.6 ± 3.6 8. 2 Remacha et al [23] Spain 128/235 CS 7.5 ± 7.8 14.3 ± 12.9 6.2% control; -B12 368.6 ± 219 Raiszadeh et al [35] United Castagna et al [29] Müller et al [30] Naisbitt et al [31] Vilaseca et al [33] Bernasconi et al [32] Remacha et al [23] de Larrañaga et al [34] Raiszadeh et al [35] Vigano et al [36] Borges-Santos et al [38] Abdollahi et al [37] Deminice et al [39] Total (95%CI) …”

Section: Outcomementioning

confidence: 99%

“…Borge s-Santos et al [38] Deminice et al [39] Larrañaga et al [34] Vigano et al [36] Vilaseca et al [33] Total (95%CI) Borges-Santos et al [38] Deminice et al [39] Larrañaga et al [34] Vilaseca et al [33] Total ( patients who were exposed to ART compared to patients who were not exposed to ART. In addition, HIVinfected patients presented decreased plasma levels of folate, but not vitamin B12.…”

Section: Studymentioning

confidence: 99%

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Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

Deminice

Silva

Oliveira

2015

WJV

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AIM:To evaluate the association between the levels of homocysteine (Hcy), folate, vitamin B12 in human immunodeficiency virus (HIV)-infected patients who were treated with antiretroviral therapy (ART) or not treated with ART. METHODS:The PubMed and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes (1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and; (2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevMan (version 5.2) was employed for data synthesis. RESULTS:A total of 12 studies were included in outcome 1 (1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy (2.05 µmol/L; 95%CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations (-2.74 ng/mL; 95%CI: -5.18 to -0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis (1167 participants; 404 HIVinfected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to non-ART HIV subjects (4.13 µmol/L; 95%CI: 1.34 to 6.92, P < 0.01). CONCLUSION:This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection. 147 META-ANALYSIS

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Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients

Roca

Girones

2016

HIV Clinical Trials

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Plasma homocysteine levels in HIV-infected men with and without lipodystrophy

Cited by 9 publications

References 34 publications

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients

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