Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide
Apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, exhibits anti-atherogenic effects similar to high-density lipoprotein (HDL). However, it remains elusive whether D-4F and HDL share similar molecular mechanisms underlying anti-atherogenic effects and endothelial cell protections. We here compared t...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2019-07-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00817/full |
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doaj-1864ad7988a1451ca4cdef2fd94b81e8 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenqi Xu Mingming Qian Caihua Huang Pengfei Cui Wei Li Qian Du Shenghui Yi Xiaohe Shi Yansong Guo Jianlan Zheng Donghui Liu Donghui Liu Donghai Lin |
spellingShingle |
Wenqi Xu Mingming Qian Caihua Huang Pengfei Cui Wei Li Qian Du Shenghui Yi Xiaohe Shi Yansong Guo Jianlan Zheng Donghui Liu Donghui Liu Donghai Lin Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide Frontiers in Pharmacology high-density lipoprotein apoA-I mimetic peptide oxidized low-density lipoprotein endothelial cell metabolomics |
author_facet |
Wenqi Xu Mingming Qian Caihua Huang Pengfei Cui Wei Li Qian Du Shenghui Yi Xiaohe Shi Yansong Guo Jianlan Zheng Donghui Liu Donghui Liu Donghai Lin |
author_sort |
Wenqi Xu |
title |
Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide |
title_short |
Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide |
title_full |
Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide |
title_fullStr |
Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide |
title_full_unstemmed |
Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide |
title_sort |
comparison of mechanisms of endothelial cell protections between high-density lipoprotein and apolipoprotein a-i mimetic peptide |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-07-01 |
description |
Apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, exhibits anti-atherogenic effects similar to high-density lipoprotein (HDL). However, it remains elusive whether D-4F and HDL share similar molecular mechanisms underlying anti-atherogenic effects and endothelial cell protections. We here compared the metabolic changes in endothelial cells induced by D-4F and HDL against oxidized low-density lipoprotein (ox-LDL), which may be of benefit to understanding the protective mechanisms of HDL and D-4F. Functional assays, including wound healing, transwell migration, and tube formation, were used to evaluate the pro-angiogenic effects of HDL and D-4F. NMR-based metabolomic analysis was employed to explore the protective mechanisms underlying HDL and D-4F. Partial least-squares discriminant analysis (PLS-DA) was performed to assess metabolic profiles, and orthogonal PLS-DA (OPLS-DA) was carried out to identify characteristic metabolites. Moreover, significantly altered metabolic pathways were also analyzed. We found that ox-LDL impaired the migration and tube formation of endothelial cells. Metabolomic analysis showed that ox-LDL triggered oxidative stress, impaired glycolysis, and enhanced glycerophospholipid metabolism. Both HDL and D-4F improved the migration and angiogenesis of endothelial cells, alleviated oxidative stress, and ameliorated disordered glycolysis impaired by ox-LDL. Strikingly, HDL partially attenuated the disturbed glycerophospholipid metabolism, whereas D-4F did not show this effect. In summary, although D-4F shared the similar protective effects with HDL on the migration and angiogenesis of endothelial cells, it could not deduce the molecular mechanisms of HDL completely. Nevertheless, D-4F possesses the potentiality to be exploited as clinically applicable agent for endothelial cell protection and cardiovascular disease treatment. |
topic |
high-density lipoprotein apoA-I mimetic peptide oxidized low-density lipoprotein endothelial cell metabolomics |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00817/full |
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doaj-1864ad7988a1451ca4cdef2fd94b81e82020-11-25T01:57:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-07-011010.3389/fphar.2019.00817449914Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic PeptideWenqi Xu0Mingming Qian1Caihua Huang2Pengfei Cui3Wei Li4Qian Du5Shenghui Yi6Xiaohe Shi7Yansong Guo8Jianlan Zheng9Donghui Liu10Donghui Liu11Donghai Lin12Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, ChinaDepartment of Cardiology, The Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, ChinaExercise and Health Laboratory, Xiamen University of Technology, Xiamen, ChinaKey Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, ChinaDepartment of Cardiology, The Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, ChinaDepartment of Cardiology, The Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, ChinaKey Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, ChinaKey Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, ChinaDepartment of Cardiology, Fujian Provincial Hospital, Provincial Clinical Medicine College, Fujian Cardiovascular Institute, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Medical University, Fuzhou, ChinaDepartment of Ob/Gyn and Neonatal and Reproductive Medicine, The People’s Liberation Army 174th Hospital and The Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Cardiology, The Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, ChinaDepartment of Cardiology, Fujian Provincial Hospital, Provincial Clinical Medicine College, Fujian Cardiovascular Institute, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Medical University, Fuzhou, ChinaKey Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, ChinaApolipoprotein A-I (apoA-I) mimetic peptide, D-4F, exhibits anti-atherogenic effects similar to high-density lipoprotein (HDL). However, it remains elusive whether D-4F and HDL share similar molecular mechanisms underlying anti-atherogenic effects and endothelial cell protections. We here compared the metabolic changes in endothelial cells induced by D-4F and HDL against oxidized low-density lipoprotein (ox-LDL), which may be of benefit to understanding the protective mechanisms of HDL and D-4F. Functional assays, including wound healing, transwell migration, and tube formation, were used to evaluate the pro-angiogenic effects of HDL and D-4F. NMR-based metabolomic analysis was employed to explore the protective mechanisms underlying HDL and D-4F. Partial least-squares discriminant analysis (PLS-DA) was performed to assess metabolic profiles, and orthogonal PLS-DA (OPLS-DA) was carried out to identify characteristic metabolites. Moreover, significantly altered metabolic pathways were also analyzed. We found that ox-LDL impaired the migration and tube formation of endothelial cells. Metabolomic analysis showed that ox-LDL triggered oxidative stress, impaired glycolysis, and enhanced glycerophospholipid metabolism. Both HDL and D-4F improved the migration and angiogenesis of endothelial cells, alleviated oxidative stress, and ameliorated disordered glycolysis impaired by ox-LDL. Strikingly, HDL partially attenuated the disturbed glycerophospholipid metabolism, whereas D-4F did not show this effect. In summary, although D-4F shared the similar protective effects with HDL on the migration and angiogenesis of endothelial cells, it could not deduce the molecular mechanisms of HDL completely. Nevertheless, D-4F possesses the potentiality to be exploited as clinically applicable agent for endothelial cell protection and cardiovascular disease treatment.https://www.frontiersin.org/article/10.3389/fphar.2019.00817/fullhigh-density lipoproteinapoA-I mimetic peptideoxidized low-density lipoproteinendothelial cellmetabolomics |