Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3 inflammasome activation in LPS-induced vascular injury.
10.1016/j.apsb.2019.02.008
- Author:
Xing ZHOU
1
;
Yanjiao WU
1
;
Lifeng YE
1
;
Yunting WANG
1
;
Kaimin ZHANG
1
;
Lingjun WANG
2
;
Yi HUANG
3
;
Lei WANG
1
;
Shaoxiang XIAN
2
;
Yang ZHANG
4
;
Yang CHEN
1
Author Information
1. School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
2. The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510407, China.
3. Department of Stomatology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
4. Department of Pharmacological & Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA.
- Publication Type:Journal Article
- Keywords:
Aspirin;
Endothelium cells;
Gap junction protein;
HMGB1;
NLRP3 inflammasome
- From:
Acta Pharmaceutica Sinica B
2019;9(4):711-723
- CountryChina
- Language:English
-
Abstract:
The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.
