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Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine

BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to exa...

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Autores principales: Xie, Xinya, Zhang, Zihui, Wang, Xinfeng, Luo, Zhenyu, Lai, Baochang, Xiao, Lei, Wang, Nanping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016886/
https://www.ncbi.nlm.nih.gov/pubmed/30134790
http://dx.doi.org/10.1186/s10020-018-0010-0
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author Xie, Xinya
Zhang, Zihui
Wang, Xinfeng
Luo, Zhenyu
Lai, Baochang
Xiao, Lei
Wang, Nanping
author_facet Xie, Xinya
Zhang, Zihui
Wang, Xinfeng
Luo, Zhenyu
Lai, Baochang
Xiao, Lei
Wang, Nanping
author_sort Xie, Xinya
collection PubMed
description BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. METHODS: The effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) were measured by using Multi Myograph System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 3′, 5′ cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western blotting. RESULTS: STA effectively blocked Hcy-induced impairment of endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs. CONCLUSION: We demonstrated that STA effectively reversed the Hcy-induced endothelial dysfunction and prevented eNOS uncoupling by increasing the expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which STA exerts its beneficial vascular effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0010-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-60168862018-07-05 Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine Xie, Xinya Zhang, Zihui Wang, Xinfeng Luo, Zhenyu Lai, Baochang Xiao, Lei Wang, Nanping Mol Med Research Article BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. METHODS: The effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) were measured by using Multi Myograph System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 3′, 5′ cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western blotting. RESULTS: STA effectively blocked Hcy-induced impairment of endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs. CONCLUSION: We demonstrated that STA effectively reversed the Hcy-induced endothelial dysfunction and prevented eNOS uncoupling by increasing the expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which STA exerts its beneficial vascular effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0010-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-19 /pmc/articles/PMC6016886/ /pubmed/30134790 http://dx.doi.org/10.1186/s10020-018-0010-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Xie, Xinya
Zhang, Zihui
Wang, Xinfeng
Luo, Zhenyu
Lai, Baochang
Xiao, Lei
Wang, Nanping
Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title_full Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title_fullStr Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title_full_unstemmed Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title_short Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine
title_sort stachydrine protects enos uncoupling and ameliorates endothelial dysfunction induced by homocysteine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016886/
https://www.ncbi.nlm.nih.gov/pubmed/30134790
http://dx.doi.org/10.1186/s10020-018-0010-0
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