Articles: apolipoproteins-e.
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J. Pharmacol. Exp. Ther. · Oct 2015
A Novel Arginase Inhibitor Derived from Scutellavia indica Restored Endothelial Function in ApoE-Null Mice Fed a High-Cholesterol Diet.
Elevated endothelial arginase activity decreases nitric oxide (NO) production by competing with the substrate l-arginine, previously reported, and reciprocally regulating endothelial nitric oxide synthase (eNOS) activity. Thus, arginase inhibitors may help treat vascular diseases associated with endothelial dysfunction. A screening of metabolites from medicinal plants revealed that (2S)-5,2',5'-trihydroxy-7,8-dimethoxy flavanone (TDF) was a noncompetitive inhibitor of arginase. ⋯ TDF incubation induced eNOS dimerization and phosphorylation at Ser1177. In addition, TDF improved Ach-dependent vasorelaxation responses and attenuated U46619-dependent contractile responses but did not change sodium nitroprusside-induced vasorelaxation or N-NAME-induced vasoconstriction. The findings suggest that TDF may help treat cardiovascular diseases by reducing pathophysiology derived from HCD-mediated endothelial dysfunction.
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The current study aimed to explore the effects of apolipoprotein e (ApoE) on intracellular calcium ([Ca(2+)]i) and apoptosis of neurons after mechanical injury in vitro. ⋯ Compared with ApoE3-treatment and WT neurons, ApoE4 caused higher intracellular calcium levels and apoptosis rates of neurons after mechanical injury. This suggested APOE polymorphisms may affect neuron apoptosis after mechanical injury through different influences on intracellular calcium levels.
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We recently reported that apolipoprotein E (ApoE)-deficient mice with a mutation in the fibrillin-1 gene (ApoE(-/-)Fbn1(C1039G+/-)) develop accelerated atherosclerosis with enhanced inflammation, atherosclerotic plaque rupture, myocardial infarction and sudden death. In the brain, fibrillin-1 functions as an attachment protein in the basement membrane, providing structural support to the blood-brain barrier (BBB). Here, we investigated whether fibrillin-1 impairment affects the permeability of the BBB proper and the blood-cerebrospinal fluid barrier (BCSFB), and whether this leads to the accelerated accumulation of lipids (xanthomas) in the brain. ⋯ Xanthomas were mainly located in fibrillin-1-rich regions, such as the choroid plexus and the neocortex. Our findings demonstrate that dysfunctional fibrillin-1 impairs BBB/BCSFB integrity, facilitating peripheral leukocyte infiltration, which further degrades the BBB/BCSFB. As a consequence, lipoproteins can enter the brain, resulting in accelerated formation of xanthomas.
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Controlled Clinical Trial
Disrupted fatty acid distribution in HDL and LDL according to apolipoprotein E allele.
Omega-3 polyunsaturated fatty acid (ω-3 PUFA) metabolism seems to be disrupted in carriers of the epsilon 4 allele of apolipoprotein E (E4+). The objective of this study was to investigate whether the ω-3 PUFA distribution in the high and low density lipoproteins is APOE-genotype dependant before and after supplementation with ω-3 PUFAs. ⋯ Contrary to what we anticipated, ω-3 PUFAs content? in HDL and LDL were not APOE isoform-dependant in young participants. However, young E4+ participants already had a tendency toward lower baseline-DHA levels in LDL particles as well as a more atherogenic ω-6/ω-3 PUFA ratio in LDL pre- and post-supplementation.