Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease

Attia, Nebil; Nakbi, Amel; Smaoui, M.; Chaaba, R.; Moulin, Philippe; Hammami, S.; Hamda, Khaldoun Ben; Chanussot, F.; Hammami, Mohamed

doi:10.1620/tjem.213.129

Cited by 27 publications

(9 citation statements)

References 50 publications

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“…We measured the cholesterol esterification rate as an assay of ‘endogenous’ LCAT that is also influenced by the endogenous lipoproteins, but found no evidence of a difference between cases and controls. Prior studies have demonstrated an inverse association between PLTP activity and cholesterol efflux capacity 22 . We measured PLTP activity and found no significant differences between the two groups.…”

Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

Agarwala

Rodrigues

Risman

et al. 2015

ATVB

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Objective Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared to controls with similarly high HDL-C and no CAD. Approach 55 subjects with very high HDL-C (mean 86 mg/dL) and onset of CAD around age 60 with no known risk factors for CAD (‘cases’) were identified through systematic recruitment. 120 control subjects without CAD, matched for race, gender, and HDL-C level (‘controls’), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. Results HDL phospholipid composition was significantly lower in cases (92 ± 37 mg/dL) than in controls (109 ± 43 mg/dL, p= 0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96 ± 0.39) compared with controls (2.11 ± 0.43, p= 0.04). Conclusions In persons with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity is associated with the paradoxical development of CAD.

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Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

Agarwala

Rodrigues

Risman

et al. 2015

ATVB

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“…De Vries et al reported that cholesterol efflux from fibroblasts to the HDL from normotriglyceridemic diabetic plasma is unchanged, while efflux to HDL by the source of hypertriglyceridemic diabetic plasma is enhanced, with concomitant increased plasma PLTP activity [44]. However, Attia et al indicated that in diabetic patients with or without CHD, PLTP activity was consistently increased in comparison with the control group [45]. …”

Section: Pltp In Cholesterol Efflux/reverse Cholesterol Transportmentioning

confidence: 99%

The impact of phospholipid transfer protein (PLTP) on lipoprotein metabolism

Jin

Hussain

2012

Nutr Metab (Lond)

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It has been reported that phospholipid transfer protein (PLTP) is an independent risk factor for human coronary artery disease. In mouse models, it has been demonstrated that PLTP overexpression induces atherosclerosis, while its deficiency reduces it. PLTP is considered a promising target for pharmacological intervention to treat atherosclerosis. However, we must still answer a number of questions before its pharmaceutical potential can be fully explored. In this review, we summarized the recent progresses made in the PLTP research field and focused on its effect on apoB-containing- triglyceride-rich particle and HDL metabolism.

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“…PLTP expression is up‐regulated in cholesterol‐laden macrophages and is present in atherosclerotic plaques (8, 9). Increased PLTP activity is seen in patients with diabetes (10) and obesity (11) and is associated with impaired cellular cholesterol efflux (12) and atherosclerosis development (13, 14). In addition to its role on lipoprotein metabolism, PLTP can exert potent anti‐inflammatory effects in macrophages by acting via ABCA1 to induce signal transducer and activator of transcription 3 (STAT3) signaling (15).…”

mentioning

confidence: 99%

Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation

et al. 2014

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Phospholipid transfer protein (PLTP) regulates phospholipid transport in the circulation and is highly expressed within the lung epithelium, where it is secreted into the alveolar space. Since PLTP expression is increased in chronic obstructive pulmonary disease (COPD), this study aimed to determine how PLTP affects lung signaling and inflammation. Despite its increased expression, PLTP activity decreased by 80% in COPD bronchoalveolar lavage fluid (BALF) due to serine protease cleavage, primarily by cathepsin G. Likewise, PLTP BALF activity levels decreased by 20 and 40% in smoke-exposed mice and in the media of smoke-treated small airway epithelial (SAE) cells, respectively. To assess how PLTP affected inflammatory responses in a lung injury model, PLTP siRNA or recombinant protein was administered to the lungs of mice prior to LPS challenge. Silencing PLTP at baseline caused a 68% increase in inflammatory cell infiltration, a 120 and 340% increase in ERK and NF-κB activation, and increased MMP-9, IL1β, and IFN-γ levels after LPS treatment by 39, 140, and 190%, respectively. Conversely, PLTP protein administration countered these effects in this model. Thus, these findings establish a novel anti-inflammatory function of PLTP in the lung and suggest that proteolytic cleavage of PLTP by cathepsin G may enhance the injurious inflammatory responses that occur in COPD.

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Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease

Cited by 27 publications

References 50 publications

High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

The impact of phospholipid transfer protein (PLTP) on lipoprotein metabolism

Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation

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