Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide

Xu, Wenqi; Qian, Mingming; Huang, Caihua; Cui, Pengfei; Li, Wei; Du, Qian; Yi, Shenghui; Shi, Xiaohe; Guo, Yujin; Zheng, Jinbao; Liu, Donghui; Lin, Donghai

doi:10.3389/fphar.2019.00817

Cited by 17 publications

(17 citation statements)

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“…Findings from our study show that metabolites involved in the glycerophospholipid metabolism pathway may also play a relevant role in pediatric hypertension. Glycerophospholipid metabolism pathway comprising two different routes, one toward phosphatidylethanolamine and the other toward phosphatidylcholine, has been shown to be a potential metabolic footprint of generation of reactive oxygen species in endothelial cells [ 27 ]. The disturbance of this pathway can trigger endothelial cell dysfunction and the development of atherosclerotic lesions [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Glycerophospholipid metabolism pathway comprising two different routes, one toward phosphatidylethanolamine and the other toward phosphatidylcholine, has been shown to be a potential metabolic footprint of generation of reactive oxygen species in endothelial cells [ 27 ]. The disturbance of this pathway can trigger endothelial cell dysfunction and the development of atherosclerotic lesions [ 27 ]. In previous studies involving adult populations, phosphatidylethanolamine has been reported as a marker for hypertension, chronic kidney disease, and CVD [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification of Potential Metabolic Markers of Hypertension in Chinese Children

Sun

Zhao

Yang

et al. 2021

International Journal of Hypertension

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Background. Studies in adults have shown that several metabolites across multiple pathways are strongly associated with hypertension. However, as yet, to our knowledge, no study has investigated such association in childhood. We, therefore, compared the serum metabolite profile of children with normal and elevated blood pressure (BP) to identify potential metabolic markers and pathways that could be useful for the assessment of pediatric hypertension. Methods. The study included 26 hypertensive children (age range, 6–11 years) and 26 age- and sex-matched ones with normal BP, who were recruited from the baseline survey of the Huantai Childhood Cardiovascular Health Cohort Study. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was performed to assess the serum metabolite profile. Logistic regression analysis was used to select significant metabolites associated with hypertension after adjustment for body mass index, waist circumference, and lipid profile. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites. Results. A total of 45 and 34 metabolites were preliminarily screened in positive and negative modes, respectively (variable importance in the projection (VIP) > 1.0 and P < 0.05 ). After adjustment for the false discovery rate, 7 and 1 differential metabolites in the positive and negative modes, respectively, remained significant (VIP > 1.0 and q < 0.05). These metabolites were mainly involved in amino acid metabolism and glycerophospholipid metabolism. Among these, two significant metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate displayed an area under the curve value of 0.820 (95% confidence interval, 0.688–0.951), with a sensitivity of 0.846 and a specificity of 0.769. Conclusion. The untargeted metabolomics approach effectively identified the differential serum metabolite profile in children with and without hypertension. Notably, two metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate exhibited a good discriminative ability to identify children with hypertension, providing new insights into potential mechanisms of pediatric hypertension.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of Potential Metabolic Markers of Hypertension in Chinese Children

Sun

Zhao

Yang

et al. 2021

International Journal of Hypertension

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“…Furthermore, D-4F decreases the myocardial infarction area in hyperglycemia mice through promoting NO release and decreasing ROS generation in endothelial cells [167]. Metabolomic analysis showed that D-4F alleviates ox-LDL-induced oxidative stress and abnormal glycolysis in endothelial cells [168].…”

Section: Apoa-i Mimetic Peptidesmentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

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High-density lipoprotein (HDL) is a heterogeneous particle composed of apolipoproteins, enzymes, and lipids. Besides transporting cholesterol to the liver, HDL also exerts many protections on anti-oxidation, anti-inflammation, and anti-apoptosis. Initial understandings of HDL came from its protective roles against atherosclerosis and the observation that high plasma HDL cholesterol (HDL-C) levels seemed to decrease cardiovascular disease (CVD) attack. However, those patients either with cholesterol ester transfer protein (CETP) deficiency or taking CETP inhibitors substantially elevated HDL-C levels but did not necessarily decrease CVD risk. Thus, some researchers suggested that quantitative measurements of HDL particle (HDL-P) might be more valuable than traditional HDL-C measurements. What is more bewildering is that HDL from patients with systemic inflammation decreased its protective effects and even became a pro-inflammatory factor. Recently, synthesized HDL and apolipoprotein mimetic peptides showed biological functions similar to native ones. Expectedly, lots of novel measurement methods and therapeutic agents about HDL would be established soon.

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“…D-4F is one of the apoA-I mimetic peptides, which shares similar structure and function with native apoA-I and provides remarkable protection to endothelial cells ( Navab et al, 2010 ). The metabolomic analysis demonstrated that D-4F alleviates oxidized low-density lipoprotein (ox-LDL)–induced oxidative stress and abnormal glycolysis in endothelial cells ( Xu et al, 2019 ). D-4F promotes the activation of endothelial nitric oxide synthase (eNOS) and the generation of NO in coronary artery endothelial cells, thus protecting against ischemia/reperfusion injuries in mice ( Baotic et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway

Guo

Qian

et al. 2021

Front. Pharmacol.

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Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI.

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Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide

Cited by 17 publications

References 60 publications

Identification of Potential Metabolic Markers of Hypertension in Chinese Children

Identification of Potential Metabolic Markers of Hypertension in Chinese Children

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway

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