Biomedicine & Pharmacotherapy (Sep 2023)
CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway
- Yunqi Liu,
- Jiapan Wang,
- Xiuye Zhao,
- Wen Li,
- Yaohua Liu,
- Xingda Li,
- Dan Zhao,
- Jie Yu,
- Hongyu Ji,
- Bing Shao,
- Zhendong Li,
- Jia Wang,
- Yilian Yang,
- Yan Hao,
- Yuting Wu,
- Ye Yuan,
- Zhimin Du
Affiliations
- Yunqi Liu
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Jiapan Wang
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Xiuye Zhao
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Wen Li
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Yaohua Liu
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Xingda Li
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Dan Zhao
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Jie Yu
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Hongyu Ji
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Bing Shao
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Zhendong Li
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Jia Wang
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Yilian Yang
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Yan Hao
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Yuting Wu
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
- Ye Yuan
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; National key laboratory of frigid cardiovascular disease, Harbin, China; Corresponding authors at: Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China.
- Zhimin Du
- Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; National key laboratory of frigid cardiovascular disease, Harbin, China; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China; Corresponding authors at: Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China.
- Journal volume & issue
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Vol. 165
p. 115267
Abstract
Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.
