High-density lipoproteins during sepsis: from bench to bedside

Tanaka, Sébastien; Couret, David; Tran-Dinh, Alexy; Duranteau, Jacques; Montravers, Philippe; Schwendeman, Anna; Meilhac, Olivier

doi:10.1186/s13054-020-02860-3

Cited by 133 publications

(169 citation statements)

References 107 publications

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“…In this study, HDL-C levels of adult COVID-19 patients were lower than normal at admission, which was similar to previous researches. Several studies showed infected patients, especially those with sepsis, always had a signi cant drop in HDL levels [10,12,15,20,21,22], but the reason for the decline in HDL level remained unexplained. However, several hypotheses are considered to be possible, including a decrease in HDL synthesis, overconsumption or redistribution of HDL particles from intravascular to the extravascular space [10,23].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have found that HDL-C can bind and neutralize the biological toxicity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) [32,33,34]. In different experimental septic models, infusion of reconstituted HDL reduced in ammation, decreased bacterial count, attenuated organ injury and improved survival [10,35,36], which greatly encouraged the application of HDL in sepsis treatment in the future. However, the role of HDL-C in viral infection remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Low high-density lipoprotein level is correlated with the severity of COVID-19 patients

Wang

Zhang

Dong

et al. 2020

Preprint

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Background The aim of the present study was to describe the clinical characteristics of patients with different levels of high-density lipoproteins (HDLs) and analyze the correlation between HDL levels and prognosis of coronavirus disease 2019 (COVID-19) patients. Methods In the clinical retrospective analysis, a total of 228 adult COVID-19 patients admitted to Public Health Treatment Center of Changsha, China from January 17 to March 14, 2020 were enrolled. Median with interquartile range and Mann-Whitney test were used to depict and analyze the clinical characteristics of patients. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between HDLs and severe events of COVID-19 patients. Results Median levels of high-density lipoprotein cholesterol (HDL-C) in adult COVID-19 patients were below normal range. Compared with patients with high HDL-C, patients with low HDL-C showed higher proportion of male (69.6% vs 45.6%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P = 0.000) and alanine aminotransferase (ALT) (median, 21.49 vs 18.81 U/L, P = 0.044), as well as higher proportion of severe events (37.0% vs 14.8%, P = 0.001). Moreover, they presented a higher risk of developing severe events compared with those with high HDL-C (Log Rank P < 0.001, Fig. 1). After adjusting for age, gender and underlying diseases, patients with low HDL-C still had elevated possibility of developing to severe cases than those with high HDL-C (HR 2.852, 95% CI 1.505–5.407, P = 0.001). Conclusions HDL-C level decreased in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low high-density lipoprotein level is correlated with the severity of COVID-19 patients

Wang

Zhang

Dong

et al. 2020

Preprint

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“…Previous studies have revealed that serum ApoA1 was associated with the outcome of patients with sepsis and acute respiratory distress syndrome induced by pneumonia, as well as critically ill patients [13][14][15][16]. In acute in ammatory disease, serum amyloid A (SAA), an acute phase protein, displaces ApoA1 from the HDL complex; then, free ApoA1 is easily eliminated by the kidney, resulting in low levels in the peripheral blood [17]. On the other hand, liver is susceptible to attack by SARS-CoV-2, especially in severe cases [18]; therefore, reduced synthesis by the injured liver may also play a role.…”

Section: Discussionmentioning

confidence: 99%

A Preliminary Study on Blood Lipid Profile in Patients with COVID-19

Zhu

Yang

Fan

et al. 2020

Preprint

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Background: Recently, dyslipidemia was observed in the patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the blood lipid profile in the patients with COVID-19, and explore their predictive value for COVID-19 severity.Methods: 142 consecutive patients with COVID-19 admitted to HwaMei Hospital, University of Chinese Academy of Sciences, from January 23 to April 20, 2020, and 77 age- and gender-matched healthy subjects were included in this retrospective study. The blood lipid profile in the patients with COVID-19 were investigated, and their predictive values for COVID-19 severity were analysed.Results: There were 125 and 17 cases in the non-severe and severe group, respectively. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) gradually decreased across healthy controls, non-severe group, and severe group. ApoA1 was recognized as an independent risk factor for COVID-19 severity，and had the highest area under the receiver operator characteristic curve (AUC) among all the single markers (AUC: 0.896, 95% CI: 0.834-0.941). Moreover, the risk model established using ApoA1 and IL-6 enhanced the prediction efficiency (AUC: 0.977, 95% CI: 0.932-0.995). Conclusion: The blood lipid profile in the patients with COVID-19 is quite abnormal from healthy subjects, especially in the severe cases. Serum ApoA1 might serve as a good indictor to reflect the severity of COVID-19.

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“…Septic patients exhibit a marked reduction in plasma HDL level and the low level of HDL cholesterol is a poor prognostic factor for severe sepsis [10][11][12]. In addition, an adverse transition of HDL to pro-inflammation was observed during acute inflammatory disorder diseases including sepsis [13][14][15]. Previous studies indicated that the abnormal oxidation of apoA-I by the myeloperoxidase (MPO) could be one of potential causes for the adverse transition of HDL in acute phase [13,16].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, an adverse transition of HDL to pro-inflammation was observed during acute inflammatory disorder diseases including sepsis [13][14][15]. Previous studies indicated that the abnormal oxidation of apoA-I by the myeloperoxidase (MPO) could be one of potential causes for the adverse transition of HDL in acute phase [13,16]. However, due to the complexity of HDL subfractions, the adverse remodeling of HDL in pathogenesis of septic ARDS is large unknown.…”

Section: Introductionmentioning

confidence: 99%

The adverse alterations of HDL in quality promote septic ARDS via exacerbated pulmonary endothelial dysfunction

Liu¹,

Liu²,

Han³

et al. 2020

Preprint

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Background Septic acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic ARDS patients are large unknown. Method To investigate HDL remodeling in septic ARDS, we analyzed composition changes of plasma HDL from 40 patients with septic ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction. Results ARDS patients showed significant changes of HDL composition, accompanied with the dramatic decrease in plasma HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, this deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the deregulation of plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression. Conclusions Our results depicted a sepsis induced remodeling in HDL quality, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.

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High-density lipoproteins during sepsis: from bench to bedside

Cited by 133 publications

References 107 publications

Low high-density lipoprotein level is correlated with the severity of COVID-19 patients

Low high-density lipoprotein level is correlated with the severity of COVID-19 patients

A Preliminary Study on Blood Lipid Profile in Patients with COVID-19

The adverse alterations of HDL in quality promote septic ARDS via exacerbated pulmonary endothelial dysfunction

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