PMID- 35397636
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 8
IP  - 1
DP  - 2022 Apr 9
TI  - Ibandronate promotes autophagy by inhibiting Rac1-mTOR signaling pathway in vitro 
      and in vivo.
PG  - 186
LID - 10.1038/s41420-022-00995-6 [doi]
LID - 186
AB  - We previously reported that ibandronate (IBAN) could improve endothelial function 
      in spontaneously hypertensive rats. However, the mechanism by which IBAN improves 
      endothelial function is unclear. The IBAN-induced autophagic process in vitro 
      experiments were determined by detection of LC3, Beclin1, and P62 protein levels 
      via western blotting. The autophagy flux was detected by confocal microscopy and 
      transmission electron microscopy. For in vivo experiments, spontaneously 
      hypertensive rats were orally administered with IBAN. Utilizing angiotensin II 
      (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and 
      human pulmonary microvascular endothelial cells (HPMECs) as a model of 
      endothelial cell injury in hypertension, we found that IBAN promoted autophagy 
      and protected cell viability in Ang II-treated-endothelial cells while these 
      effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN 
      treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) 
      pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. 
      Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy 
      by downregulating Rac1-mTOR. Taken together, our results firstly revealed that 
      IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus 
      alleviates Ang II-induced injury in endothelial cells.
CI  - (c) 2022. The Author(s).
FAU - Han, Jie
AU  - Han J
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Yang, Jian
AU  - Yang J
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Wang, Qiqi
AU  - Wang Q
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Yin, Xiang
AU  - Yin X
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Sun, Zewei
AU  - Sun Z
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Huang, Chaoyang
AU  - Huang C
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Chen, Guoping
AU  - Chen G
AD  - Department of Endocrinology, The First Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou, China.
FAU - Zheng, Liangrong
AU  - Zheng L
AD  - Department of Cardiology and Atrial Fibrillation Center, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Jiang, Dongmei
AU  - Jiang D
AUID- ORCID: 0000-0001-9597-6986
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, Zhejiang, China. 3312024@zju.edu.cn.
LA  - eng
GR  - 81701365/National Science Foundation of China | National Natural Science 
      Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/
GR  - LY20H020004,No.Z16H020002,LY19H020008/Natural Science Foundation of Zhejiang 
      Province (Zhejiang Provincial Natural Science Foundation)/
PT  - Journal Article
DEP - 20220409
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC8994753
COIS- The authors declare no competing interests.
EDAT- 2022/04/11 06:00
MHDA- 2022/04/11 06:01
PMCR- 2022/04/09
CRDT- 2022/04/10 20:10
PHST- 2021/09/21 00:00 [received]
PHST- 2022/03/25 00:00 [accepted]
PHST- 2022/03/23 00:00 [revised]
PHST- 2022/04/10 20:10 [entrez]
PHST- 2022/04/11 06:00 [pubmed]
PHST- 2022/04/11 06:01 [medline]
PHST- 2022/04/09 00:00 [pmc-release]
AID - 10.1038/s41420-022-00995-6 [pii]
AID - 995 [pii]
AID - 10.1038/s41420-022-00995-6 [doi]
PST - epublish
SO  - Cell Death Discov. 2022 Apr 9;8(1):186. doi: 10.1038/s41420-022-00995-6.