Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms

Ghosh, Alip; Murugesan, Gurunathan; Chen, Kan; Zhang, Li; Wang, Qing; Febbraio, Maria; Anselmo, Rita Marie; Marchant, Kandice; Barnard, John; Silverstein, Roy L.

doi:10.1182/blood-2011-02-338582

Cited by 93 publications

(94 citation statements)

References 50 publications

(68 reference statements)

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“…The rs1761665 SNP, in particular, is in strong LD with promoter SNPs previously shown to influence monocyte and platelet CD36 (58,59). Several of the promoter SNPs we identified here lie in close proximity to validated binding sites for PPAR and to methylation sites that associate with CD36 mRNA levels (Fig.…”

Section: 11supporting

confidence: 51%

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Love‐Gregory

Kraja

Allum

et al. 2016

Journal of Lipid Research

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Elevated fasting lipid levels have traditionally been associated with increased risk of heart disease, diabetes, and stroke. More recently, similar and independent associations were found with levels of nonfasting or postprandial lipids (1, 2). Nonfasting measurements incorporate those of chylomicrons (CMs) produced in response to dietary fat Abstract Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a 410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPAR, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce

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Section: 11supporting

confidence: 51%

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Love‐Gregory

Kraja

Allum

et al. 2016

Journal of Lipid Research

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“…Notable exceptions have been reported by Himoto et al (25) and García-Monzón et al (26) who identified even lower sCD36 concentrations compared to those from the current study (Table IV). This variation could be population-specific as cellular CD36 expression may be associated with the inheritance of specific CD36 gene polymorphisms (27,28). Additionally, cellular CD36 expression can be affected by other factors including fat intake (29) and blood glucose levels (30).…”

Section: Discussionmentioning

confidence: 99%

Soluble cluster of differentiation 36 concentrations are not associated with cardiovascular risk factors in middle-aged subjects

et al. 2016

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Abstract. Cluster of differentiation 36 (CD36) is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized low-density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and possibly acted as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. The present study was conducted to further investigate the association between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. sCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patient medical records. sCD36 concentrations were relatively low compared to the majority of other studies and were not significantly different between the MetS group and controls (P=0.17). sCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. sCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease, and those without these abnormalities (P>0.05). The inconsistency between results reported in the present study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36 + microparticles if it was to be used as a biomarker. IntroductionCardiovascular disease (CVD) is the principal cause of fatalities among older adults worldwide (1). Advanced age, male gender and family history of CVD are considered as non-modifiable cardiovascular risk factors (2). Alternatively, modifiable risk factors for CVD include obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol, diabetes mellitus (DM), smoking and a sedentary lifestyle (3). To best identify the subjects at an increased risk of CVD, the term 'Metabolic Syndrome' (MetS) emerged to describe a cluster of the modifiable risk factors that they can predict the occurrence of CVD when they exist together (4). However, subjects are diagnosed with MetS when they fulfill certain criteria that were defined by several health organizations (5-8).Certain subjects may develop CVD without having numerous cardiovascular risk factors (9). Khot et al (10) have shown that at least one of the four traditional risk factors (smoking, DM, hyperlipidemia and hypertension) was found in ~80% of thei...

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“…Triolein and oleic acid were added at varying concentrations to double distilled water. Concentrations used ranged from 0.0009 w/v% to 5 w/v% for oleic acid and from 0.006 w/v % to 31.7w/v % for triolein and were prepared in quarter-log dilution steps. All preparations were mixed with 5% (w/v) Gum Arabica (AEP Colloids, Hadley, NY) and white food colorant was added to produce perceptually identical viscosity and color between oil and control samples.…”

Section: Preparation Of Oleic Acid and Triolein Emulsions Preparationmentioning

confidence: 99%

The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects

Pepino

Love‐Gregory

Klein

et al. 2012

Journal of Lipid Research

248

226

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Obesity is caused by ingesting more energy than is expended over a long period of time. Dietary fat is the most energy-dense macronutrient, and its overconsumption has been linked to obesity ( 1-4 ). Obese people prefer foods with higher fat content ( 5 ), crave high-fat foods more frequently ( 6, 7 ), and consume more fat than lean individuals ( 8 ).Traditionally, perception of fat in the oral cavity is thought to rely almost entirely on textural and aromatic cues activating the somatosensory and olfactory systems. However, there is now increasing evidence to support an important role of the gustatory system in fat perception ( 9-20 ) as well as in intestinal lipid metabolism ( 10, 21 ). Oral and gastrointestinal fat sensory sensitivity appear to be associated ( 16 ) and there is similarity in the chemosensory reception events and their signaling transduction pathways in the tongue and gastrointestinal tract ( 21 ). An important requirement for the involvement of a gustatory component in dietary lipid detection is the hydrolysis of triacylglycerols (TGs) to release free FAs, the signaling stimulus, as was demonstrated through the use of the lipase inhibitor orlistat ( 22 ). In rodents, lingual lipase is essential for the gustatory perception of dietary fats ( 22 ) and the addition of orlistat to fat emulsions diminishes the rat's preference for TG, but not FA ( 22 ). Although it is not known whether lingual lipase is important for oral fat perception in humans, data from a recent study suggests that lingual lipase lipolytic activity can produce FA within the concentration range required to activate oral sensors ( 18 ).Several putative fat taste receptor classes have been identifi ed in rodents ( 12,23,24 ), including the glycoprotein CD36 ( 25 ). The presence of CD36, a scavenger receptor that mediates uptake and traffi cking of lipids in diverse cell types ( 26 ), has been documented in the gustatory papillae of rodents ( 25, 27 ), pigs, and humans ( 28 ). In rodents, the interaction between CD36 and FA results in signaling events that depend on an intact neuronal gustatory pathway ( 15,29 ). CD36 gene knockout impedes fat detection in mice without affecting sweet or bitter perception Abstract The precise orosensory inputs engaged for dietary lipids detection in humans are unknown. We evaluated whether a common single nucleotide polymorphism (rs1761667) in the CD36 gene that reduces CD36 expression and the addition of orlistat, a lipase inhibitor, to reduce FA release from triacylglycerols (TGs), the main component of dietary fats, would attenuate fat orosensory sensitivity in humans. Twenty-one obese subjects with different rs1761667 genotypes (6 AA, 7 AG, and 8 GG) were studied on two occasions in which oleic acid and triolein orosensory detection thresholds were measured using emulsions prepared with and without orlistat. Subjects homozygous for the G-allele had 8-fold lower oral detection thresholds for oleic acid and triolein than subjects homozygous for the A allele, which associates with lower CD36 expr...

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Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms

Cited by 93 publications

References 50 publications

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Soluble cluster of differentiation 36 concentrations are not associated with cardiovascular risk factors in middle-aged subjects

The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects

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