Relationship between Microbial Translocation and Endothelial Function in HIV Infected Patients

Blodget, Emily; Shen, Changyu; Aldrovandi, Grace M.; Rollie, Adrienne; Gupta, Samir K.; Stein, James H.; Dubé, Michael P.

doi:10.1371/journal.pone.0042624

Cited by 45 publications

(37 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…108 In addition, it was recently shown that FMD of the brachial artery was independently associated with plasma LPS levels in patients receiving ART. 109 Taken together, these findings suggest that microbial translocation might indeed contribute to endothelial dysfunction in both treated and untreated HIV infection.…”

Section: Endothelial Dysfunctionmentioning

confidence: 85%

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

Trøseid

Manner

Pedersen

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial translocation and cardiovascular risk factors will translate into increased risk of acute events, and whether strategies to target gut microbiota and microbial translocation might reduce such a risk.

show abstract

Section: Endothelial Dysfunctionmentioning

confidence: 85%

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

Trøseid

Manner

Pedersen

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…Plasma for lipopolysaccharide (LPS) was quantified using the Endpoint Chromogenic LAL assay (Lonza, Basel, Switzerland) 34 .…”

Section: Methodsmentioning

confidence: 99%

Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation

Sattler

Letendre³

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

Self Cite

View full text Add to dashboard Cite

Objective We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Design Cross-sectional Setting Six Academic Centers Participants 152 patients with plasma HIV RNA <1,000copies/ml had clinical evaluations and cognitive function quantified by global deficit scores (GDS). Outcome Measures GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. Results WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year of the index visit, GDS remained worse in patients with IL-6 levels in the high-versus-low tertile (p=0.02). Path analysis to explore potential mediators of NCI produced a strong, integrated model for patients in the high CSF sCD40L tertile. In this model, WC affected GDS both directly and via a second path that was mediated by IL-6. Inclusion of plasma sCD14 levels strengthened the model. NCI was more common in men and for individuals with components of the metabolic syndrome. Conclusions NC function was significantly linked to abdominal obesity, systemic inflammation (high IL-6), and immune activation in plasma (high sCD14) and CSF (high sCD40L). Abdominal obesity, inflammation, and CNS immune activation are potential therapeutic targets for NCI in HIV+ patients.

show abstract

“…13 We recently reported impaired vascular endothelial function associated with greater LPS levels among HIV-infected subjects receiving long-term ART. 14 In mice, mimicking the translocation of gut bacterial products into the circulation via subcutaneous infusion of LPS has been shown to increase fasting glucose and insulin levels, liver insulin resistance, and body weight. These changes were accompanied by increases in visceral and subcutaneous adipose deposition, and greater liver triglyceride content.…”

Section: Introductionmentioning

confidence: 99%

Microbial Translocation and Metabolic and Body Composition Measures in Treated and Untreated HIV Infection

Timmons

Shen

Aldrovandi

et al. 2014

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N = 49 on antiretroviral therapy (ART), N = 47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N = 82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r = 0.19, p = 0.02), particularly in the 5152s ART-naive cohort (r = 0.41, p < 0.01). Triglycerides were correlated with LPS in the combined cohort (r = 0.32, p < 0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r = -0.21, p < 0.01), as well as the IU subset not on ART (r = -0.32, p = 0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r = -0.18, p = 0.02), particularly among the IU subset receiving ART (r = -0.33, p = 0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.

show abstract

Relationship between Microbial Translocation and Endothelial Function in HIV Infected Patients

Cited by 45 publications

References 29 publications

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation

Microbial Translocation and Metabolic and Body Composition Measures in Treated and Untreated HIV Infection

Contact Info

Product

Resources

About