Dataset Information

The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

ABSTRACT: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH).A total of 118 HeFH, 6 HoFH, and 117 controls were included in the study. Plasma PCSK9 and apoB-48 concentrations were measured in the fasting state.Plasma PCSK9 and apoB-48 levels were higher in FH subjects compared with controls (PCSK9: HoFH: 642.6 ± 246.9 vs. HeFH: 324.9 ± 119.8 vs.194.5 ± 65.9 ng/mL, P < 0.0001; apoB-48: HoFH: 14.71 ± 4.36 vs. HeFH: 6.55 ± 4.24 vs.3.03 ± 2.07 ?g/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (? = 0.06, P = 0.5) and HeFH subjects (? = 0.07, P = 0.4). Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001).These data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels.NCT02225340 .

SUBMITTER: Drouin-Chartier JP

PROVIDER: S-EPMC5472856 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

Drouin-Chartier Jean-Philippe JP Hogue Jean-Charles JC Tremblay André J AJ Bergeron Jean J Lamarche Benoît B Couture Patrick P

Lipids in health and disease 20170615 1

<h4>Background</h4>Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a lar ...[more]

PMID: 28619117

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Project description:ObjectiveDyslipidemia is implicated in abdominal aortic aneurysms (AAAs) in humans and angiotensin (Ang) II-infused mice. This study determined effects of major lipoprotein classes on AngII-induced AAAs using multiple mouse strains with dietary and pharmacological manipulations.Approach and resultsWestern diet had minor effects on plasma cholesterol concentrations and the low incidence of AngII-induced AAAs in C57BL/6J mice. Low incidence of AAAs in this strain was not attributed to protection from high-density lipoprotein, because apolipoprotein (apo) AI deficiency did not increase AngII-induced AAAs. ApoAI deletion also failed to alter AAA occurrence in hypercholesterolemic mice. Low-density lipoprotein receptor-/- mice fed normal diet had low incidence of AngII-induced AAAs. Western diet feeding of this strain provoked pronounced hypercholesterolemia because of increased apoB-containing lipoproteins with attendant increases of atherosclerosis in both sexes, but AAAs only in male mice. ApoE-deficient mice fed normal diet were modestly hypercholesterolemic, whereas this strain fed Western diet was severely hypercholesterolemic because of increased apoB-containing lipoprotein concentrations. The latter augmented atherosclerosis, but did not change the high incidence of AAAs in this strain. To determine whether reductions in apoB-containing lipoproteins influenced AngII-induced AAAs, ezetimibe was administered at a dose that partially reduced plasma cholesterol concentrations to ApoE-deficient mice fed Western diet. This decreased atherosclerosis, but not AAAs. This ezetimibe dose in ApoE-deficient mice fed normal diet significantly decreased plasma apoB-containing lipoprotein concentrations and reduced AngII-induced AAAs.ConclusionsApoB-containing lipoproteins contribute to augmentation of AngII-induced AAA in male mice. However, unlike atherosclerosis, AAA occurrence was not correlated with increases in plasma apoB-containing lipoprotein concentrations.

Dataset Information

The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

Publications

The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

Similar Datasets

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