HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

Tabet, Fatiha; Vickers, Kasey C.; Torres, Luisa; Wiese, Carrie B.; Shoucri, Bassem M.; Lambert, Gilles; Catherinet, Claire; Prado-Lourenço, Leonel; Levin, Michael G.; Thacker, Seth G.; Sethupathy, Praveen; Barter, Philip J.; Remaley, Alan T.; Rye, Kerry Anne

doi:10.1038/ncomms4292

Cited by 354 publications

(331 citation statements)

References 70 publications

(75 reference statements)

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“…120 HDL was shown to deliver miR-223 into endothelial cells, where it downregulates expression of intracellular cell adhesion molecule 1 (ICAM-1). 121 However, these findings are in contrast to those by Wagner et al 10 who confirmed the presence of low copy numbers of miRNAs in HDL, but found no evidence that HDL delivers physiologically relevant amounts of miRNAs into endothelial cells, smooth muscle cells, and peripheral blood mononuclear cells. 10 In general, it is important to emphasize the low concentration of miRNAs in HDL, which is beyond particle concentration.…”

Section: Sphingolipidsmentioning

confidence: 68%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

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Section: Sphingolipidsmentioning

confidence: 68%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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“…Population studies elucidated HDLs as an independent inverse predictor of cardiovascular disease 30, 31. These epidemiologic findings were confirmed in vitro and in animal models, as supported by promotion of cholesterol efflux from cells or tissues,32 inhibition of vascular inflammation33, and improved endothelial cell function 34. Whereas most studies reported the relationship between circulating ANGPTL4 levels and HDL‐c, they mainly recruited Europeans,8, 14 American,12 or Hispanic subjects 35.…”

Section: Discussionmentioning

confidence: 85%

Angiopoietin‐Like Protein 4 Is a High‐Density Lipoprotein (HDL) Component for HDL Metabolism and Function in Nondiabetic Participants and Type‐2 Diabetic Patients

Yang

Wang

et al. 2017

JAHA

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Background ANGPTL4 (angiopoietin‐like protein 4) is a LPL (lipoprotein lipase) inhibitor and is present in high‐density lipoprotein (HDL). However, it is not defined whether ANGPTL4 in HDLs could affect HDL metabolism and function in type 2 diabetes mellitus (T2DM).Methods and Results ANGPTL4 levels in the circulation and HDLs were quantified in nondiabetic participants (n=201, 68.7% females) and T2DM patients (n=185, 66.5% females). HDLs were isolated from nondiabetic controls and T2DM patients to assess cholesterol efflux or subjected to endothelial lipase (EL)‐overexpressed HEK293 cells for EL hydrolysis in vitro. The association between ANGPTL4 in HDLs and HDL components and function was analyzed in nondiabetic participants or diabetic patients, respectively. Plasma or HDLs of ANGPTL4+/+ and ANGPTL4−/− mice was subjected for cholesterol efflux or EL hydrolysis, respectively. ANGPTL4 levels in the plasma and HDLs were 1.7‐ and 2.0‐fold higher in T2DM patients than nondiabetic controls, respectively (P<0.0001). Multivariable analysis demonstrated that per 1 doubling increase of ANGPTL4 levels in HDLs, the changes amounted to +0.27% cholesterol efflux (P=0.03), +0.06 μg/mL apolipoprotein A‐I (P=0.09) and −9.41 μg/L serum amyloid A (P=0.02) in nondiabetic controls. In T2DM patients, the corresponding estimates were −0.06% cholesterol efflux (P=0.10), −0.06 μg/mL apolipoprotein A‐I (P=0.38), and +3.64 μg/L serum amyloid A (P=0.72). HDLs isolated from ANGPTL4−/− mice showed accelerated hydrolysis by EL and reduced cholesterol efflux compared with ANGPTL4+/+ littermates.ConclusionsPhysically, ANGPTL4 in HDLs protected HDLs from hydrolysis. Resulting from increased circulating ANGPTL4 levels in T2DM, ANGPTL4 levels in HDLs were elevated but with compromised inhibitory effect on EL, leading to increased HDL hydrolysis and dysfunction.

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“…Tabet et al . (2014) demonstrated that miR‐223 is transferred from native HDL to endothelial cells and HDL inhibits expression of intercellular adhesion molecule 1 (ICAM‐1) through the transfer of miR‐223 to endothelial cells. All these findings support that HDL‐miRNA delivery is a new mechanism of miRNA transport.…”

Section: How Cells Communicatementioning

confidence: 99%

Cell‐to‐cell communication: microRNAs as hormones

2017

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Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell‐to‐cell communication within the tumor microenvironment. EVs’ components, such as proteins, noncoding RNAs [microRNAs (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and lipids, can mediate paracrine signaling in the tumor microenvironment. Recently, miRNAs encapsulated in secreted EVs have been identified in the extracellular space. Mature miRNAs that participate in intercellular communication are released from most cells, often within EVs, and disseminate through the extracellular fluid to reach remote target cells, including tumor cells, whose phenotypes they can influence by regulating mRNA and protein expression either as tumor suppressors or as oncogenes, depending on their targets. In this review, we discuss the roles of miRNAs in intercellular communication, the biological function of extracellular miRNAs, and their potential applications for diagnosis and therapeutics. We will give examples of miRNAs that behave as hormones.

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HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

Cited by 354 publications

References 70 publications

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Angiopoietin‐Like Protein 4 Is a High‐Density Lipoprotein (HDL) Component for HDL Metabolism and Function in Nondiabetic Participants and Type‐2 Diabetic Patients

Cell‐to‐cell communication: microRNAs as hormones

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