High-Density Lipoprotein Reduces the Human Monocyte Inflammatory Response

Murphy, Andrew; Woollard, Kevin J.; Hoang, Anh; Mukhamedova, Nigora; Stirzaker, Roslynn A.; McCormick, Sally P.A.; Remaley, Alan T.; Sviridov, Dmitri; Chin-Dusting, Jaye

doi:10.1161/atvbaha.108.168690

Cited by 445 publications

(425 citation statements)

References 49 publications

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“…Moreover, HDL serves a protective role against systemic inflammation by removing oxidized phospholipids and fatty acids from LDL, VLDL, and IDL, removing endotoxin and serum amyloid-A from the circulation 17,18 , and promoting their disposal in the liver. Finally, normal HDL inhibits the attachment of monocytes to endothelial cells by inhibiting expression of vascular cell adhesion mol ecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells 19,20 and CD11b on monocytes 21 (FIG. 2).…”

Section: Biologic Functions Of Normal Hdlmentioning

confidence: 99%

HDL abnormalities in nephrotic syndrome and chronic kidney disease

2015

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| Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.

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Section: Biologic Functions Of Normal Hdlmentioning

confidence: 99%

HDL abnormalities in nephrotic syndrome and chronic kidney disease

2015

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“…The role played by lipoproteins in modulating membrane cholesterol content has recently been subject to extensive investigations and has led to the suggestion that these molecules may have immunomodulatory functions (Norata et al 2012;Murphy et al 2008Murphy et al , 2011Carpintero et al 2010;Gruaz et al 2010;Landry et al 2006). In particular, high-density lipoproteins (HDLs) have been shown to modulate the innate immune response by decreasing the production of inflammatory mediators, as well regulating adaptive immunity either by inhibiting antigen presentation or by altering the cholesterol content of LRs to alter T cell activation and signaling.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Larbi

Fortin

Dupuis

et al. 2014

AGE

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Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.

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“…High‐density lipoproteins (HDLs) have systemic anti‐inflammatory and antioxidant properties and limit endothelial dysfunction and damage by attenuating endothelial cell activation and adhesion molecule expression, by activating endothelial nitric oxide synthase, and by promoting endothelial repair 10, 13, 14, 15, 16, 17, 18, 19, 20. In critically ill patients with pneumonia or sepsis, low HDL cholesterol concentrations are associated with multiorgan dysfunction and short‐ and long‐term death 21, 22.…”

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confidence: 99%

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.Methods and ResultsWe tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003).ConclusionsA higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

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High-Density Lipoprotein Reduces the Human Monocyte Inflammatory Response

Abstract: HDL and apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through several receptors.

Cited by 445 publications

References 49 publications

HDL abnormalities in nephrotic syndrome and chronic kidney disease

HDL abnormalities in nephrotic syndrome and chronic kidney disease

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

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