Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro

Angelovich, Thomas A; Hearps, Anna C.; Oda, Michael N.; Borja, Mark S.; Huynh, Diana; Homann, Stefanie; Jaworowski, Anthony; Kelesidis, Theodoros

doi:10.1097/qad.0000000000001642

Cited by 14 publications

(15 citation statements)

References 12 publications

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“…Infection not only leads to a decrease in HDL levels, but also affects its function. HDL from HIV+ individuals has reduced antioxidant function (Angelovich et al, 2017), modified HDL metabolism, and reduced functionality of reverse cholesterol transport (Rose et al, 2008). In mice models, HDL loses its anti-inflammatory properties after acute influenza infection (Van Lenten et al, 2001).…”

Section: Changes In Levels or Functions Of Hdlmentioning

confidence: 99%

The Role of High-Density Lipoprotein in COVID-19

Wang

Deng

et al. 2021

Front. Pharmacol.

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The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge. Managing a large number of acutely ill patients in a short time, whilst reducing the fatality rate and dealing with complications, brings unique difficulties. The most striking pathophysiological features of patients with severe COVID-19 are dysregulated immune responses and abnormal coagulation function, which can result in multiple-organ failure and death. Normally metabolized high-density lipoprotein (HDL) performs several functions, including reverse cholesterol transport, direct binding to lipopolysaccharide (LPS) to neutralize LPS activity, regulation of inflammatory response, anti-thrombotic effects, antioxidant, and anti-apoptotic properties. Clinical data shows that significantly decreased HDL levels in patients with COVID-19 are correlated with both disease severity and mortality. However, the role of HDL in COVID-19 and its specific mechanism remain unclear. In this analysis, we review current evidence mainly in the following areas: firstly, the pathophysiological characteristics of COVID-19, secondly, the pleiotropic properties of HDL, thirdly, the changes and clinical significance of HDL in COVID-19, and fourthly the prospect of HDL-targeting therapy in COVID-19 to clarify the role of HDL in the pathogenesis of COVID-19 and discuss the potential of HDL therapy in COVID-19.

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Section: Changes In Levels or Functions Of Hdlmentioning

confidence: 99%

The Role of High-Density Lipoprotein in COVID-19

Wang

Deng

et al. 2021

Front. Pharmacol.

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“…We have isolated HDL particles from plasma obtained from a limited number of virologically suppressed PLWH, incorporated the isolated particles into the atherosclerotic plaque model and showed that they promote foam cell formation by monocytes from healthy, HIV-negative individuals. This behavior was associated with defective redox properties of the HDL particles (134). Functional defects in HDL particles isolated from PLWH have been reported by others, specifically a decreased level of the enzymes Paraoxonase (PON) 1 and 3 and a decreased level of PON redox activity (135).…”

Section: Abnormal Lipoproteins In Plwh May Influence Monocyte Behaviormentioning

confidence: 99%

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

et al. 2019

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Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.

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“…Importantly, the readout from this assay has also been reported to be associated with established proinflammatory and proatherogenic phenotypes of HDL (Kelesidis et al, 2014) and was able to predict the direct ex vivo proatherogenic potential of dysfunctional HDL (its ability to promote monocyte-derived foam cell formation [MDFCF], a key event in early atherogenesis; Angelovich et al, 2017). HDL isolated from HIV+ patients with an otherwise low CVD risk profile, who were taking potent ART [HIV(+)HDL] had reduced antioxidant function and increased lipid peroxide content (HDLox) and promoted ex vivo MDFCF to a greater extent than HDL isolated from healthy individuals (33.0% vs. 26.2% foam cells; Angelovich et al, 2017). There is limited data regarding how different measures of HDL function (such as impaired antioxidant function) other than the impaired HDL-C efflux may contribute to clinical CVD.…”

Section: Introductionmentioning

confidence: 99%

High‐density lipoprotein lipid peroxidation as a molecular signature of the risk for developing cardiovascular disease: Results from MASHAD cohort

Samadi

Mehramiz

Kelesidis

et al. 2019

Journal Cellular Physiology

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High‐density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three‐hundred and thirty individuals who had a median follow‐up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41–1.86; p < 0.001). For every increase in HDLox by 0.1 unit, there was an increase in CVD risk by 1.62‐fold. In an adjusted analysis, there was a >2.5‐fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox > 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88–3.94). Higher HDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population‐based cohort.

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Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro

Cited by 14 publications

References 12 publications

The Role of High-Density Lipoprotein in COVID-19

The Role of High-Density Lipoprotein in COVID-19

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

High‐density lipoprotein lipid peroxidation as a molecular signature of the risk for developing cardiovascular disease: Results from MASHAD cohort

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