PMID- 31541678
OWN - NLM
STAT- MEDLINE
DCOM- 20200902
LR  - 20200902
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 145
DP  - 2019 Dec
TI  - Protective effects of acarbose against vascular endothelial dysfunction through 
      inhibiting Nox4/NLRP3 inflammasome pathway in diabetic rats.
PG  - 175-186
LID - S0891-5849(19)31010-X [pii]
LID - 10.1016/j.freeradbiomed.2019.09.015 [doi]
AB  - The cardiovascular efficacy of glucose-lowering drugs is needed due to the 
      cardiovascular complication in type 2 diabetes mellitus (T2DM). Acarbose is an 
      alpha-glucosidase inhibitor that suppresses postprandial hyperglycemia, however, the 
      cardiovascular protection of acarbose has still remained controversial. NLRP3 
      inflammasome activation mediated tight junction disruption, a hallmark event of 
      endothelial barrier dysfunction leading to endothelial hyperpermeability in 
      diabetes. Given the anti-inflammatory property of acarbose, it was investigated 
      that acarbose protected against vascular endothelial barrier dysfunction through 
      inhibiting NLRP3 inflammasome in vascular endothelial cells in T2DM rats. The rat 
      aortic endothelial cells (RAECs) were incubated with high glucose (HG, 30 mM) for 
      24 h in vitro. It was found that HG significantly induced the formation and 
      activation of NLRP3 inflammasome, which was markedly blocked by acarbose 
      treatment. Furthermore, acarbose blocked the Nox4-dependent superoxide (O(2)(.-)) 
      generation, which regulated NLRP3 inflammasome in RAECs. Importantly, we found 
      that acarbose remarkably enhanced the junction protein expression of ZO-1 and 
      VE-Cadherin and consequently abolished vascular hyperpermeability, which was 
      associated with inhibiting NLRP3 inflammasome in RAECs. In vivo, acarbose 
      intervention relieved vascular leakage in the heart of diabetic rats injected 
      with Evans blue dye and the vasodilatory response to acetylcholine, which was 
      accompanied with the restoration of ZO-1, VE-Cadherin, Nox4 and NLRP3 
      inflammasome in the aortal endothelium of diabetic rats. Taken together, our data 
      indicated that acarbose ameliorated endothelial barrier dysfunction by directly 
      inhibiting NLRP3 inflammasome which was dependent on inhibiting Nox4 
      oxidase-dependent O(2)(.-) production. These properties might carry a potential 
      significance for acarbose in cardiovascular protection in diabetic patients.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Li, Xiao-Xue
AU  - Li XX
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China.
FAU - Ling, Sun-Kai
AU  - Ling SK
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China.
FAU - Hu, Ming-Yue
AU  - Hu MY
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China.
FAU - Ma, Yu
AU  - Ma Y
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China.
FAU - Huang, Pei-Lin
AU  - Huang PL
AD  - Department of Pathology and Pathophysiology, Southeast University School of 
      Medicine, Nanjing, 210009, China. Electronic address: seu1580@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190918
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (Nox4 protein, rat)
RN  - IY9XDZ35W2 (Glucose)
RN  - T58MSI464G (Acarbose)
SB  - IM
MH  - Acarbose/*pharmacology
MH  - Animals
MH  - Cardiovascular Diseases/complications/*drug therapy/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism/pathology
MH  - Disease Models, Animal
MH  - Endothelial Cells/drug effects/pathology
MH  - Glucose/metabolism
MH  - Humans
MH  - Inflammasomes/genetics/metabolism
MH  - NADPH Oxidase 4/*genetics
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*genetics
MH  - Rats
MH  - Reactive Oxygen Species
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Acarbose
OT  - Diabetes
OT  - NLRP3 inflammasome
OT  - Nox4
OT  - Vascular permeability
EDAT- 2019/09/22 06:00
MHDA- 2020/09/04 06:00
CRDT- 2019/09/22 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/09/01 00:00 [revised]
PHST- 2019/09/17 00:00 [accepted]
PHST- 2019/09/22 06:00 [pubmed]
PHST- 2020/09/04 06:00 [medline]
PHST- 2019/09/22 06:00 [entrez]
AID - S0891-5849(19)31010-X [pii]
AID - 10.1016/j.freeradbiomed.2019.09.015 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2019 Dec;145:175-186. doi: 
      10.1016/j.freeradbiomed.2019.09.015. Epub 2019 Sep 18.