期刊
JCI INSIGHT
卷 7, 期 2, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.145475
关键词
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资金
- National Natural Science Foundation of China [81873486, 81770327]
- Clinical Medicine Expert Team (Class A) of Jinji Lake Health Talents Program of Suzhou Industrial Park [SZYQTD202102]
- Suzhou Key Discipline for Medicine [SZXK202129]
- Demonstration of Scientific and Technological Innovation Project [SKY2021002]
- Suzhou Dedicated Project on Diagnosis and Treatment Technology of Major Diseases [LCZX202132]
- Research on Collaborative Innovation of medical engineering combination [SZM2021014]
There is a high prevalence of ventricular arrhythmias related to sudden cardiac death in patients with chronic kidney disease (CKD). The study found that indoxyl sulfate (IS) reduces Ito,f-related proteins and Ito,f density by activating ROS/MAPK and NF-KB signaling pathways, leading to prolonged action potential duration and QT interval, which increases the susceptibility to arrhythmia in CKD patients.
There is a high prevalence of ventricular arrhythmias related to sudden cardiac death in patients with chronic kidney disease (CKD). To explored the possible mechanism of CKD-related ventricular arrhythmias, a CKD rat model was created, and indoxyl sulfate (IS) was further used in vivo and in vitro. This project used the following methods: patch clamp, electrocardiogram, and some molecular biology experimental techniques. IS was found to be significantly elevated in the serum of CKD rats. Interestingly, the expression levels of the fast transient outward potassium current- related (Ito,f-related) proteins (Kv4.2, Kv4.3, and KChIP2) in the heart of CKD rats and rats treated with IS decreased. IS dose-dependently reduced Ito,f density, accompanied by the decreases in Kv4.2, Kv4.3, and KChIP2 proteins in vitro. IS also prolonged the action potential duration and QT interval, and paroxysmal ventricular tachycardia could be induced by IS. In-depth studies have shown that ROS/p38MAPK, ROS-p44/42 MAPK, and NF-KB signaling pathways play key roles in the reduction of Ito,f density and Ito,f-related proteins caused by IS. These data suggest that IS reduces Ito,f-related proteins and Ito,f density by activating ROS/MAPK and NF-KB signaling pathways, and the action potential duration and QT interval are subsequently prolonged, which contributes to increasing the susceptibility to arrhythmia in CKD.
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