9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and...

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Autores principales:	Yan-Mei Wang, Shou-Ling Mi, Hong Jin, Qi-Lin Guo, Zhong-Yu Yu, Jian-Tao Wang, Xiao-Ming Zhang, Qian Zhang, Na-Na Wang, Yan-Yan Huang, Hou-Guang Zhou, Jing-Chun Guo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	diabetic cardiovascular complications autophagy 9-PAHSA myocardial hypertrophy vascular calcification Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5d63894a25794b2a80922871f5ba2fea
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spelling	oai:doaj.org-article:5d63894a25794b2a80922871f5ba2fea2021-11-15T06:54:03Z9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice1663-981210.3389/fphar.2021.754387https://doaj.org/article/5d63894a25794b2a80922871f5ba2fea2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.754387/fullhttps://doaj.org/toc/1663-9812Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.Yan-Mei WangShou-Ling MiHong JinQi-Lin GuoZhong-Yu YuJian-Tao WangXiao-Ming ZhangQian ZhangNa-Na WangYan-Yan HuangHou-Guang ZhouJing-Chun GuoFrontiers Media S.A.articlediabetic cardiovascular complicationsautophagy9-PAHSAmyocardial hypertrophyvascular calcificationTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic cardiovascular complications autophagy 9-PAHSA myocardial hypertrophy vascular calcification Therapeutics. Pharmacology RM1-950
spellingShingle	diabetic cardiovascular complications autophagy 9-PAHSA myocardial hypertrophy vascular calcification Therapeutics. Pharmacology RM1-950 Yan-Mei Wang Shou-Ling Mi Hong Jin Qi-Lin Guo Zhong-Yu Yu Jian-Tao Wang Xiao-Ming Zhang Qian Zhang Na-Na Wang Yan-Yan Huang Hou-Guang Zhou Jing-Chun Guo 9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
description	Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.
format	article
author	Yan-Mei Wang Shou-Ling Mi Hong Jin Qi-Lin Guo Zhong-Yu Yu Jian-Tao Wang Xiao-Ming Zhang Qian Zhang Na-Na Wang Yan-Yan Huang Hou-Guang Zhou Jing-Chun Guo
author_facet	Yan-Mei Wang Shou-Ling Mi Hong Jin Qi-Lin Guo Zhong-Yu Yu Jian-Tao Wang Xiao-Ming Zhang Qian Zhang Na-Na Wang Yan-Yan Huang Hou-Guang Zhou Jing-Chun Guo
author_sort	Yan-Mei Wang
title	9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
title_short	9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
title_full	9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
title_fullStr	9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
title_full_unstemmed	9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
title_sort	9-pahsa improves cardiovascular complications by promoting autophagic flux and reducing myocardial hypertrophy in db/db mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5d63894a25794b2a80922871f5ba2fea
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9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice

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