PMID- 34867366
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220120
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - 9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and 
      Reducing Myocardial Hypertrophy in Db/Db Mice.
PG  - 754387
LID - 10.3389/fphar.2021.754387 [doi]
LID - 754387
AB  - 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.
CI  - Copyright (c) 2021 Wang, Mi, Jin, Guo, Yu, Wang, Zhang, Zhang, Wang, Huang, Zhou 
      and Guo.
FAU - Wang, Yan-Mei
AU  - Wang YM
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Mi, Shou-Ling
AU  - Mi SL
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Jin, Hong
AU  - Jin H
AD  - Shanghai Stomatological Hospital & Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
FAU - Guo, Qi-Lin
AU  - Guo QL
AD  - Department of Translational Neuroscience, Jing'an District Centre Hospital of 
      Shanghai & State Key Laboratory of Medical Neurobiology and MOE Frontiers Center 
      for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 
      China.
FAU - Yu, Zhong-Yu
AU  - Yu ZY
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Wang, Jian-Tao
AU  - Wang JT
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Zhang, Xiao-Ming
AU  - Zhang XM
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - Department of Translational Neuroscience, Jing'an District Centre Hospital of 
      Shanghai & State Key Laboratory of Medical Neurobiology and MOE Frontiers Center 
      for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 
      China.
FAU - Wang, Na-Na
AU  - Wang NN
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Huang, Yan-Yan
AU  - Huang YY
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Zhou, Hou-Guang
AU  - Zhou HG
AD  - Department of Geriatrics of Huashan Hospital, National Clinical Research Center 
      for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Guo, Jing-Chun
AU  - Guo JC
AD  - Department of Translational Neuroscience, Jing'an District Centre Hospital of 
      Shanghai & State Key Laboratory of Medical Neurobiology and MOE Frontiers Center 
      for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211115
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
EIN - Front Pharmacol. 2022 Jan 03;12:827490. PMID: 35046833
PMC - PMC8634679
OTO - NOTNLM
OT  - 9-PAHSA
OT  - autophagy
OT  - diabetic cardiovascular complications
OT  - myocardial hypertrophy
OT  - vascular calcification
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/07 06:00
MHDA- 2021/12/07 06:01
PMCR- 2021/11/15
CRDT- 2021/12/06 09:04
PHST- 2021/08/06 00:00 [received]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/12/06 09:04 [entrez]
PHST- 2021/12/07 06:00 [pubmed]
PHST- 2021/12/07 06:01 [medline]
PHST- 2021/11/15 00:00 [pmc-release]
AID - 754387 [pii]
AID - 10.3389/fphar.2021.754387 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Nov 15;12:754387. doi: 10.3389/fphar.2021.754387. 
      eCollection 2021.