Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes.
10.1007/s12264-020-00544-0
- Author:
Hong-Bin LIN
1
;
Guan-Shan WEI
1
;
Feng-Xian LI
1
;
Wen-Jing GUO
1
;
Pu HONG
1
;
Ya-Qian WENG
1
;
Qian-Qian ZHANG
1
;
Shi-Yuan XU
1
;
Wen-Bin LIANG
2
;
Zhi-Jian YOU
3
;
Hong-Fei ZHANG
4
Author Information
1. Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China.
2. University of Ottawa Heart Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, K1N, Canada.
3. Department of Anesthesiology, Shenzhen SAMII Medical Center, Shenzhen, 518118, China.
4. Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China. zhanghongfei@smu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Cardiac dysfunction;
Diabetes mellitus;
Ischemic stroke;
Macrophage;
NLRP3 inflammasome
- From:
Neuroscience Bulletin
2020;36(9):1035-1045
- CountryChina
- Language:English
-
Abstract:
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
