SR‐BI, CD36, and caveolin‐1 contribute positively to cholesterol efflux in hepatic cells

Truong, To Quyen; Aubin, Dominique; Falstrault, Louise; Brodeur, Mathieu R.; Brissette, Louise

doi:10.1002/cbf.1680

Cited by 23 publications

(20 citation statements)

References 57 publications

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“…This is in line with the well-known function of SR-BI in mediating selective lipid uptake from HDL particles. In contrast to our fi nding that SR-BI decreases cholesterol effl ux to apoA-I, a recent study demonstrated that SR-BI in hepatocytes can promote cholesterol effl ux to human HDL 3 ( 49 ). The different effects of SR-BI on cholesterol effl ux in the two studies are likely due to differences in the abilities of lipid-poor apoA-I and HDL 3 in promoting cholesterol effl ux.…”

Section: Discussioncontrasting

confidence: 99%

Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

Wroblewski

Cai

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org composition and apolipoprotein content. Numerous epidemiological studies indicate that HDL particles serve an anti-atherogenic function in that high levels of HDL cholesterol are associated with a decreased risk of atherosclerosis ( 1 ). An important atheroprotective effect of HDL is its ability to remove excess cholesterol from peripheral tissues and deliver it to the liver for biliary excretion by a process called reverse cholesterol transport (RCT) ( 2-4 ). Beyond promotion of RCT, other properties of HDL, including anti-infl ammatory, anti-oxidative, anti-thrombotic and anti-apoptotic features of HDL, also contribute to its anti-atherogenic function ( 5 ). However, the fundamental mechanisms underlying the biogenesis and maintenance of plasma HDL levels are not well understood.ABCA1 is recognized as the principal molecule involved in cholesterol effl ux from macrophage foam cells ( 6 ). It is expressed in a variety of cell types, including hepatocytes and macrophages and is highly upregulated upon lipid loading through the activation of the nuclear liver X receptors (LXR ␣ and/or LXR ␤ ) ( 7,8 ). The absence of functional ABCA1 in Tangier disease patients results in severe HDL defi ciency and deposition of cholesteryl esters (CE) in the reticulo-endothelial system ( 9-11 ). HDL defi ciency and macrophage foam cell accumulation are also found in mice lacking ABCA1 in the liver ( 12 ). The observed HDL defi ciency is a direct result of a severely impaired lipidation of apoA-I via the ABCA1 pathway; therefore, this pathway is not only important for lipid effl ux from both peripheral and hepatic cells but also for the biogenesis of nascent HDL and maintenance of plasma HDL levels ( 13 ).

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Section: Discussioncontrasting

confidence: 99%

Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

Wroblewski

Cai

et al. 2012

Journal of Lipid Research

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“…However, recent work has demonstrated that (neonatal) ventricular myocytes control cholesterol predominantly through cholesterol efflux rather than internalisation of native or acetylated LDL [11]. These authors focused on the ABC transporters as cholesterol efflux pathways, however caveolin has also been linked with cholesterol efflux to HDL [36], [37]. Here we show further evidence for a cholesterol-dependent control of efflux pathways.…”

Section: Discussionsupporting

confidence: 59%

Caveolin Contributes to the Modulation of Basal and β-Adrenoceptor Stimulated Function of the Adult Rat Ventricular Myocyte by Simvastatin: A Novel Pleiotropic Effect

et al. 2014

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The number of people taking statins is increasing across the globe, highlighting the importance of fully understanding statins' effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system (‘pleiotropic effects’). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 µM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2+]i) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to β2-, but not β1-, adrenoceptor stimulation. Under conditions of β2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16 and troponin I at Ser23/24 was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered β-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae.

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“…Other proteins have been described to contribute to cellular cholesterol efflux in different cell types, including the scavenger receptor B1 (SR-BI), CD36 and Caveolin-1 (Cav-1) [51]. However, their contribution to macrophage RCT in vivo is not clear and remains uncertain [52].…”

Section: Cholesterol Homeostasis Cholesterol Efflux and Reverse Cmentioning

confidence: 99%

“…As lipid droplet cholesteryl ester hydrolysis is being recognized as an important step in cholesterol efflux [56], miRNAs that target key pathways in lipid-loaded macrophage autophagy and/or cholesterol ester hydrolases might be interesting targets to promote cholesterol efflux. Caveolin has been proposed to contribute to cellular cholesterol efflux [51,160]. Several miRNAs including, miR-103, miR-107, miR-133a, miR-802 and others were validated to target Cav-1 [161,162].…”

Section: Mirna Targets In Cholesterol Efflux Reverse Cholesterol mentioning

confidence: 99%

From evolution to revolution: miRNAs as pharmacological targets for modulating cholesterol efflux and reverse cholesterol transport

Dávalos

Fernández‐Hernando

2013

Pharmacological Research

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There has been strong evolutionary pressure to ensure that an animal cell maintain levels of cholesterol within tight limits for normal function. Imbalances in cellular cholesterol levels are a major player in the development of different pathologies associated to dietary excess. Although epidemiological studies indicate that elevated levels of high-density lipoprotein (HDL)-cholesterol reduce the risk of cardiovascular disease, recent genetic evidence and pharmacological therapies to raise HDL levels do not support their beneficial effects. Cholesterol efflux as the first and probably the most important step in reverse cholesterol transport is an important biological process relevant to HDL function. Small non-coding RNAs (microRNAs), post-transcriptional control different aspects of cellular cholesterol homeostasis including cholesterol efflux. miRNA families miR-33, miR-758, miR-10b, miR-26 and miR-106b directly modulates cholesterol efflux by targeting the ATP-binding cassette transporter A1 (ABCA1). Pre-clinical studies with anti-miR therapies to inhibit some of these miRNAs have increased cellular cholesterol efflux, reverse cholesterol transport and reduce pathologies associated to dyslipidemia. Although miRNAs as therapy have benefits from existing antisense technology, different obstacles need to be solved before we incorporate such research into clinical care. Here we focus on the clinical potential of miRNAs as therapeutic target to increase cholesterol efflux and reverse cholesterol transport as a new alternative to ameliorate cholesterol-related pathologies.

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SR‐BI, CD36, and caveolin‐1 contribute positively to cholesterol efflux in hepatic cells

Cited by 23 publications

References 57 publications

Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

Caveolin Contributes to the Modulation of Basal and β-Adrenoceptor Stimulated Function of the Adult Rat Ventricular Myocyte by Simvastatin: A Novel Pleiotropic Effect

From evolution to revolution: miRNAs as pharmacological targets for modulating cholesterol efflux and reverse cholesterol transport

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