Lipoprotein Remnants and Endothelial Dysfunction in the Postprandial Phase

Maggi, F.M.; Raselli, Sara; Grigore, Liliana; Redaelli, L.; Fantappiè, Simona; Catapano, Alberico L.

doi:10.1210/jc.2003-031977

Cited by 69 publications

(48 citation statements)

References 44 publications

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“…Previous clinical studies have shown an acute and direct effect of hypertriglyceridemia on vascular endothelium. Acute hypertriglyceridemia induced by an oral fat load caused endothelial dysfunction in subjects with dyslipidemia 30 and increased circulatory cellular adhesion molecules in healthy subjects. 31 Further study is needed to clarify the involvement of apoCIII in this phenomenon.…”

Section: Discussionmentioning

confidence: 98%

Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction

et al. 2008

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Background-Apolipoprotein CIII (apoCIII) is a component of some triglyceride-rich very-low-density and low-density lipoprotein and is elevated in dyslipidemia with insulin resistance and the metabolic syndrome. We previously reported that apoCIII directly activates proinflammatory and atherogenic signaling in vascular endothelial cells through protein kinase C-␤ (PKC␤). Because PKC␤ impairs the response of vascular endothelial cells to insulin, we tested the hypothesis that apoCIII affects insulin signaling in vascular endothelial cells and its function in vitro and in vivo. Methods and Results-ApoCIII inhibited insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), decreasing phosphatidylinositol 3-kinase (PI3K)/Akt activation in human umbilical vein endothelial cells. These effects of apoCIII led to reduced endothelial nitric oxide synthase (eNOS) activation and NO release into the media. ApoCIII activated PKC␤ in human umbilical vein endothelial cells, resulting in IRS-1 dysfunction via serine phosphorylation. ApoCIII also activated mitogen-activated protein kinase through PKC␤. The impaired insulin signaling was restored by PKC␤ inhibitor or MEK1 inhibitor. ApoCIII-rich very-low-density lipoprotein and apoCIII impaired insulin signaling in the aorta of C57BL/6J mice and in human umbilical vein endothelial cells, which was recovered by PKC␤ inhibitor. They also inhibited endothelium-dependent relaxation of the aortas of C57BL/6J mice. In summary, apoCIII in very-low-density lipoprotein impaired insulin stimulation of NO production by vascular endothelium and induced endothelial dysfunction in vivo. This adverse effect of apoCIII was mediated by its activation of PKC␤, which inhibits the IRS-1/PI3K/Akt/eNOS pathway. Conclusion-Our

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Section: Discussionmentioning

confidence: 98%

Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction

et al. 2008

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“…The atherogenic effects of RLPs on the endothelium include upregulation of proinflammatory cytokines, monocyte recruitment and activation, and increased production of prothrombotic factors 4. Changes in RLPs in the postprandial state may lead to endothelial dysfunction as measured by flow‐mediated dilation 40. In an immunohistochemical analysis of carotid plaque after endarterectomy, RLPs were significantly associated with carotid plaque macrophage content, a surrogate for plaque instability 41.…”

Section: Discussionmentioning

confidence: 99%

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Joshi

Khokhar

Massaro

et al. 2016

JAHA

143

102

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BackgroundRemnant lipoproteins (RLPs), the triglyceride‐enriched precursors to low‐density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP‐C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and ResultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable‐adjusted hazard ratios (HRs) for RLP‐C (the sum of very low‐density lipoprotein3 cholesterol and intermediate‐density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid‐lowering therapy for the combined population, RLP‐C (HR 1.23 per 1‐SD increase, 95% CI 1.06–1.42, P<0.01) and intermediate‐density lipoprotein cholesterol (HR 1.26 per 1‐SD increase, 95% CI 1.08–1.47, P<0.01) predicted CHD during an 8‐year follow‐up. Associations were attenuated by high‐density lipoprotein cholesterol and ultimately lost significance with inclusion of real low‐density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.Conclusion RLP‐C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP‐C to prevent CHD warrant further intensive investigation.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

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“…Postprandial hyperlipidemia has been also reported to be associated with insulin resistance syndrome and an effective indicator for developing vascular complications [15]. An abnormal postprandial elevation of TG or RLP has been suggested to lead to endothelial dysfunction [16]. Delayed clearance of postprandial large TG-rich particles is reported in subjects with LPL abnormality [17].…”

Section: Discussionmentioning

confidence: 99%

Development of Cookie Test for the Simultaneous Determination of Glucose Intolerance, Hyperinsulinemia, Insulin Resistance and Postprandial Dyslipidemia

Harano¹,

Miyawaki

Nabiki

et al. 2006

Endocr J

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Abstract.A new cookie test was developed for the simultaneous evaluation of multiple risk factors such as glucose intolerance, hyperinsulinemia, insulin resistance and postprandial dyslipidemia. The cookie consisting of 75 g carbohydrate and 25 g fat is ingested and the blood samples are obtained at 0, 1 and 2 hours later. When the two carbohydrate sources, liquid glucose and test cookie, were compared as a glucose load within 3 months, the 2 hr plasma glucose levels were not statistically different, proposing the use of the same criteria at 2 hour glucose level for the diagnosis of diabetes and impaired glucose tolerance (IGT) in subjects without exocrine pancreatic dysfunction. In addition, hyperinsulinemia, insulin resistance (AUC insulin, and/or AUC insulin X AUC glucose), and postprandial hyperlipidemia (DTG, Triglyceride; DRLP, remnant like particles) have been simultaneously uncovered. Reactive hypoglycemia with adverse epigastric discomfort was observed in 26.3% of the control subjects with liquid glucose, while it was observed in only 1 case (5.3%) without any symptom with cookie tests. In fact, one reactive hypoglycemia out of 5 with liquid glucose turned out to be IGT with cookie test. In 64 subjects with lifestyle-related diseases, cookie test revealed hyperinsulinemia and insulin resistance in 56% respectively, postprandial hyperlipidemia in 39%, diabetes and IGT in 22-23% of each of the subjects and all showed at least one abnormal value. In contrast, in university students with exercise habit, all showed normal results with cookie test. In addition, improved insulin sensitivity over non-exercise group was obverved. In summary, the cookie test provided more informations compared with OGTT using liquid glucose and with fewer side effects. Simultaneous evaluation of glucose intolerance, hyperinsulinemia, insulin resistance, and postprandial hyperlipidemia was also possible. SIMULTANEOUS determination of glucose intolerance including diabetes mellitus (DM), hyperinsulinemia, insulin resistance and postprandial dyslipidemia is beneficial for the early detection of metabolic factors involved in the lifestyle-related diseases [1]. Oral glucose tolerance test (OGTT) can reveal glucose intolerance, hyperinsulinemia, and apparent insulin resistance [2], but false reactive hypoglycemia has often been observed with adverse epigastric symptoms and does not reflect the daily blood glucose excursion and insulin responses. The cookie was ingested and the blood glucose, insulin and TG or RLP responses were measured in the newly developed cookie test. With the exception of exocrine pancreatic dysfunction, starch and 15% maltose are thought to be well digested and no significant difference has been reported for the postprandial 2 hr blood glucose levels [3]. Thus after ingestion of the cookie, postprandial hyperglycemia using the same criteria as OGTT, as well as postprandial dyslipidemia can be simultaneously evaluated. Measurement of endogenous insulin gives additional information regarding hyperinsulinemia and in...

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Lipoprotein Remnants and Endothelial Dysfunction in the Postprandial Phase

Cited by 69 publications

References 44 publications

Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction

Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Development of Cookie Test for the Simultaneous Determination of Glucose Intolerance, Hyperinsulinemia, Insulin Resistance and Postprandial Dyslipidemia

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