L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling

Peripheral artery disease (PAD), primarily caused by atherosclerosis, leads to the narrowing or blockage of arteries that supply blood to the limbs. This study explores the pro-angiogenic effects of L-theanine and its underlying mechanisms in a mouse model of hindlimb ischemia (HLI). To evaluate L-...

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Main Authors: Jingyi Wang, Yinghui Xu, Yating Ruan, Xinyang Hu
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2025-01-01
Series:Biomolecules & Biomedicine
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Online Access:https://www.bjbms.org/ojs/index.php/bjbms/article/view/11256
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author Jingyi Wang
Yinghui Xu
Yating Ruan
Xinyang Hu
author_facet Jingyi Wang
Yinghui Xu
Yating Ruan
Xinyang Hu
author_sort Jingyi Wang
collection DOAJ
description Peripheral artery disease (PAD), primarily caused by atherosclerosis, leads to the narrowing or blockage of arteries that supply blood to the limbs. This study explores the pro-angiogenic effects of L-theanine and its underlying mechanisms in a mouse model of hindlimb ischemia (HLI). To evaluate L-theanine's pro-angiogenic effects, human umbilical vein endothelial cells (HUVECs) were subjected to tube formation, migration, sprouting, and proliferation assays. In vivo, C57BL/6 mice with induced HLI were treated with L-theanine. Blood flow recovery was measured via Doppler ultrasound, and vascular density was analyzed using immunofluorescence staining. RNA sequencing identified neuropilin-1 (NRP1) as a key regulator, and the expression levels of NRP1 and VEGFR2 were examined through qPCR and Western blotting. L-theanine significantly enhanced angiogenesis in HUVECs, as demonstrated by improved tube formation, migration, sprouting, and proliferation. In mice, L-theanine treatment resulted in increased vessel density and improved blood flow recovery. Furthermore, L-theanine was found to activate the NRP1/VEGFR2 signaling pathway in both HUVECs and the HLI mouse model. These findings indicate that L-theanine can promote angiogenesis and activate key pathways involved in vascular repair, suggesting its potential as a therapeutic agent for treating vascular defects associated with PAD.
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institution Kabale University
issn 2831-0896
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language English
publishDate 2025-01-01
publisher Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
record_format Article
series Biomolecules & Biomedicine
spelling doaj-art-fe30ed5402ca472baf05080d332525ce2025-01-09T16:39:09ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2025-01-0110.17305/bb.2024.11256L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signalingJingyi Wang0Yinghui Xu1Yating Ruan2Xinyang Hu3Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, ChinaDepartment of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, ChinaDepartment of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, China Peripheral artery disease (PAD), primarily caused by atherosclerosis, leads to the narrowing or blockage of arteries that supply blood to the limbs. This study explores the pro-angiogenic effects of L-theanine and its underlying mechanisms in a mouse model of hindlimb ischemia (HLI). To evaluate L-theanine's pro-angiogenic effects, human umbilical vein endothelial cells (HUVECs) were subjected to tube formation, migration, sprouting, and proliferation assays. In vivo, C57BL/6 mice with induced HLI were treated with L-theanine. Blood flow recovery was measured via Doppler ultrasound, and vascular density was analyzed using immunofluorescence staining. RNA sequencing identified neuropilin-1 (NRP1) as a key regulator, and the expression levels of NRP1 and VEGFR2 were examined through qPCR and Western blotting. L-theanine significantly enhanced angiogenesis in HUVECs, as demonstrated by improved tube formation, migration, sprouting, and proliferation. In mice, L-theanine treatment resulted in increased vessel density and improved blood flow recovery. Furthermore, L-theanine was found to activate the NRP1/VEGFR2 signaling pathway in both HUVECs and the HLI mouse model. These findings indicate that L-theanine can promote angiogenesis and activate key pathways involved in vascular repair, suggesting its potential as a therapeutic agent for treating vascular defects associated with PAD. https://www.bjbms.org/ojs/index.php/bjbms/article/view/11256peripheral artery diseasePADangiogenesisL-theanineneuropilin-1NRP1
spellingShingle Jingyi Wang
Yinghui Xu
Yating Ruan
Xinyang Hu
L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
Biomolecules & Biomedicine
peripheral artery disease
PAD
angiogenesis
L-theanine
neuropilin-1
NRP1
title L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
title_full L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
title_fullStr L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
title_full_unstemmed L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
title_short L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
title_sort l theanine promotes angiogenesis in limb ischemic mice by modulating nrp1 vegfr2 signaling
topic peripheral artery disease
PAD
angiogenesis
L-theanine
neuropilin-1
NRP1
url https://www.bjbms.org/ojs/index.php/bjbms/article/view/11256
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AT yatingruan ltheaninepromotesangiogenesisinlimbischemicmicebymodulatingnrp1vegfr2signaling
AT xinyanghu ltheaninepromotesangiogenesisinlimbischemicmicebymodulatingnrp1vegfr2signaling