Role of HDL-Associated Proteins and Lipids in the Regulation of Inflammation

White, Roger; Giordano, Samantha; Datta, Geeta

doi:10.5772/67141

Cited by 19 publications

(19 citation statements)

References 121 publications

(143 reference statements)

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“…One of the most compelling finding of this study is the association of lower baseline HDL levels with SARS-CoV-2 positivity, which corroborates an earlier study, which found association of declining HDL levels with Covid-19 disease severity (10). While causal inferences are beyond the scope of this study, given HDL’s established antioxidant, antithrombotic and anti-inflammatory characteristics, it seems plausible that HDL may play a protective role in preventing the establishment of SARS-CoV-2 infection (19). Alternatively, HDL is now known to transport a wide range of cargo other than cholesterol, such as microRNAs (miRNAs) (20).…”

Section: Discussionmentioning

confidence: 99%

Baseline Cardiometabolic Profiles and SARS-CoV-2 Risk in the UK Biobank

Scalsky

Desai

Chen

et al. 2020

Preprint

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Background SARS-CoV-2 is a rapidly spreading coronavirus with a high incidence of severe upper respiratory infection that first presented in Wuhan, China in December 2019. Many factors have been identified as risk factors for SARS-CoV-2, with much attention being paid to body mass index (BMI), but little investigation has been done to investigate dysregulation of lipid profiles and diabetes, which are often comorbid in high BMI patients. Objective This study seeks to describe the impact of BMI, HDL, LDL, ApoA, ApoB, triglycerides, hemoglobin A1c (HbA1c), diabetes, alcohol and red wine intake on SARS-CoV-2 risk in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the risk of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through June 29, 2020. Logistic regression was performed on the target variables controlling for age, sex and ancestry. Results BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 risk (p < 0.05) while HDL and ApoA were associated with decreased risk (p < 0.001). Additionally, red wine intake was associated with reduced SARS-CoV-2 risk (p < 0.05). LDL, ApoB and triglyceride levels were not found to be significantly associated with increased risk. Conclusion Elevated HDL and ApoA levels and alcohol intake, specifically red wine intake, were associated with reduced risk of testing positive for SARS-CoV-2, while type II diabetes and HbA1c were associated with increased risk. The effects of alcohol, type II diabetes and HbA1c levels may be indirect, mediated in part through regulation of HDL levels. In summary, our study corroborates the emerging picture that high HDL levels may confer protection against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Baseline Cardiometabolic Profiles and SARS-CoV-2 Risk in the UK Biobank

Scalsky

Desai

Chen

et al. 2020

Preprint

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“…Apolipoprotein A1 Major component of the High-Density Lipoprotein (HDL) complex, which is a modulator of innate immune response and inflammation (Fotakis et al, 2019;Gordon et al, 2011;Macpherson et al, 2019;White et al, 2017) . Although it might be that APOA1 levels drop upon the infection, we can also speculate that low APOA1 levels are a risk factor for COVID-19.…”

Section: Supplementary Informationmentioning

confidence: 99%

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Messner

Demichev

Wendisch

et al. 2020

Preprint

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The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks. Highlights-A completely redesigned clinical proteomics platform increases throughput and precision while reducing costs.-27 biomarkers are differentially expressed between WHO severity grades for COVID-19.-The study highlights potential therapeutic targets that include complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling both upstream and downstream of interleukin 6.

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“…It has been demonstrated that HDL-associated platelet-activating factor acetylhydrolase (PAF-AH) hampers the production and limits the activity of mildly oxidized low-density lipoprotein since it facilitates the hydrolysis of active oxidized phospholipids to lysolipids, which in consequence results in the removal of biologically active lipids in these lipoproteins [37]. ApoA-I has been shown to be the main protein constituent of HDL which binds to and removes lipid hydroperoxides of LDL both in vitro and in vivo and reduces the amount of cholesteryl ester hydroperoxides and phosphatidylcholine hydroperoxides [31,38]. The resulting oxidized HDL was demonstrated to be removed by hepatocytes more rapidly and selectively than native HDL [31].…”

Section: Hdl Role and Functionsmentioning

confidence: 99%

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

Rysz

Gluba-Brzózka

Rysz-Górzyńska

et al. 2020

IJMS

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Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.

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Role of HDL-Associated Proteins and Lipids in the Regulation of Inflammation

Cited by 19 publications

References 121 publications

Baseline Cardiometabolic Profiles and SARS-CoV-2 Risk in the UK Biobank

Baseline Cardiometabolic Profiles and SARS-CoV-2 Risk in the UK Biobank

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

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