Monocyte Activation, but not Microbial Translocation, Is Independently Associated With Markers of Endovascular Dysfunction in HIV-Infected Patients Receiving cART

Pedersen, Kim Steenstrup; Manner, Ingjerd W.; Seljeflot, Ingebjørg; Kvale, Dag; Os, Ingrid; Gerstoft, Jan; Nielsen, Susanne Dam; Trøseid, Marius

doi:10.1097/qai.0000000000000339

Cited by 15 publications

(20 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMAO interferes with reverse cholesterol transportation and promotes foam cell formation and atherosclerosis [43]. Since endothelial dysfunction is an early step in the atherosclerotic process, this association is not surprising and it fits well with our previous finding of a close association between soluble CD14 and ADMA in HIV-infected persons on cART [23]. However, it is intriguing that the correlation was driven by the group of HIV + T2D+, and the association was not significant in either HIV + T2D- or HIV-T2D+.…”

Section: Discussionsupporting

confidence: 86%

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundIncreased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD.MethodsCross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex.High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS.ResultsThe percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001).ConclusionElevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2334-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 86%

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, associations between TMAO and systemic inflammatory marker CRP or microbial translocation marker LPS were not found. Both markers are known to be volatile, and previous studies have reported lacking or weak associations between LPS and CRP and other markers of microbial translocation and systemic inflammation [40–43]. Further, interpretation of the association between sCD14 and TMAO as proof of the impact of microbial translocation on plasma TMAO cannot be inferred.…”

Section: Discussionmentioning

confidence: 94%

Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundHIV infection is associated with increased risk of cardiovascular disease beyond that explained by traditional risk factors. Altered gut microbiota, microbial translocation, and immune activation have been proposed as potential triggers. The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) predicts myocardial infarction (MI) in the general population and has recently been shown to induce platelet hyperreactivity. In the present study, we investigated if TMAO was associated with platelet function, microbial translocation, and immune activation in both untreated and combination anti-retroviral therapy (cART) HIV infection.MethodsTMAO and the pre-cursors betaine, choline, and carnitine were quantified by mass-spectrometry in plasma samples from a previously established cross-sectional cohort of 50 untreated and 50 cART treated HIV-infected individuals. Whole-blood impedance aggregometry, C-reactive protein, sCD14, and lipopolysaccharide were assessed as measures of platelet function, inflammation, monocyte activation, and microbial translocation, respectively.ResultsTMAO was not associated with platelet aggregation response after stimulation with four different agonists, or with overall hypo- or hyperreactivity in untreated or treated HIV-infected individuals. In contrast, sCD14 a marker of both monocyte activation and microbial translocation was independently associated with TMAO in untreated HIV-infection (R = 0.381, P = 0.008). Lower levels of carnitine [32.2 (28.4–36.8) vs. 38.2 (33.6–42.0), P = 0.001] and betaine [33.1 (27.3–43.4) vs.37.4 (31.5–48.7, P = 0.02], but similar TMAO levels [3.8 (2.3–6.1), vs. 2.9 μM (1.9–4.8) P = 0.15] were found in cART treated compared to untreated HIV-infected individuals, resulting in higher ratios of TMAO/carnitine [0.12 (0.07–0.20) vs. 0.08 (0.05–0.11), P = 0.02] and TMAO/betaine [0.11 (0.07–0.17) vs. 0.08 (0.05–0.13), P 0.02].ConclusionsIn contrast to recent studies in HIV-uninfected populations, the present study found no evidence of TMAO-induced platelet hyperreactivity in HIV infected individuals. Microbial translocation and monocyte activation may affect TMAO levels in untreated individuals. Furthermore, the elevated ratios of TMAO/betaine and TMAO/carnitine in cART-treated individuals could possibly suggest a role of cART in TMAO metabolism.

show abstract

“…A total of 60 PLHIV from the outpatient clinic at the Department of Infectious Diseases, Rigshospitalet, Copenhagen, were consecutively included in a study regarding cognitive function and cardiovascular risk profile, and 31 HIV-uninfected controls were selected for comparison and matched overall on age, gender, BMI, education and comorbidity index (assessed by the Charlson comorbidity index). Procedures for recruitment, data collection, demographics, and clinical characteristics of the participants have previously been described in detail [15,[35][36][37][38][39]. Nineteen of the controls also participated in a study on diabetes [40].…”

Section: Study Populationmentioning

confidence: 99%

“…Detailed information on demographic factors, medical history, smoking, physical activity, medication and data regarding HIV infection were collected at inclusion [35][36][37]. All examinations were performed by trained medical staff.…”

Section: Clinical Assessmentsmentioning

confidence: 99%

Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV

et al. 2020

Self Cite

View full text Add to dashboard Cite

People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD), and immunity against cytomegalovirus (CMV) may be a contributing factor. We hypothesized that enhanced T-cell responses against CMV and CMV-IgG antibody-levels are associated with higher arterial blood pressure in PLHIV. We assessed serum CMV-IgG, systolic-(SBP) and diastolic-(DBP) blood pressure, pulse pressure (PP), traditional risk factors, activated CD8+ T-cells (CD38+HLA-DR+), senescent CD8+ T-cells (CD28-CD57+) and interleukin-6 (IL-6) in 60 PLHIV and 31 HIV-uninfected controls matched on age, gender, education and comorbidity. In PLHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65 and CMV-gB. Associations between CMV-specific immune responses and hypertension, SBP, DBP or PP were assessed by multivariate logistic and linear regression models adjusted for appropriate confounders. The median age of PLHIV was 47 years and 90% were male. Prevalence of hypertension in PLHIV was 37% compared to 55% of HIV-uninfected controls. CMV-specific CD8+ T-cell responses were independently associated with higher PP (CMV-pp65; β = 2.29, p = 0.001, CMV-gB; β = 2.42, p = 0.001) in PLHIV. No significant differences were found with regard to individual measures of SBP and DBP. A possible weak association was found between CMV-IgG and hypertension (β = 1.33, p = 0.049) after adjustment for age, smoking and LDL-cholesterol. HIV-related factors, IL-6, CD8+ Tcell activation or CD8+ T-cell senescence did not mediate the associations, and no associations were found between CMV-specific CD4+ T-cell responses and blood pressure in PLHIV. In conclusion, increased arterial blood pressure in PLHIV may be affected by heightened CMV-specific CD8+ T-cell responses.

show abstract

Monocyte Activation, but not Microbial Translocation, Is Independently Associated With Markers of Endovascular Dysfunction in HIV-Infected Patients Receiving cART

Abstract: Monocyte activation as measured by sCD14 is associated with endovascular dysfunction in HIV infection.

Cited by 15 publications

References 32 publications

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection

Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV

Contact Info

Product

Resources

About