caa a22 4500 606158472 CHVBK 20210128100619.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10557-015-6598-1 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6598-1 Valsartan Upregulates Kir2.1 in Rats Suffering from Myocardial Infarction via Casein Kinase 2 [Elektronische Daten] [Xinran Li, Hesheng Hu, Ye Wang, Mei Xue, Xiaolu Li, Wenjuan Cheng, Yongli Xuan, Jie Yin, Na Yang, Suhua Yan] Purpose: Myocardial infarction (MI) results in an increased susceptibility to ventricular arrhythmias, due in part to decreased inward-rectifier K+ current (IK1), which is mediated primarily by the Kir2.1 protein. The use of renin-angiotensin-aldosterone system antagonists is associated with a reduced incidence of ventricular arrhythmias. Casein kinase 2 (CK2) binds and phosphorylates SP1, a transcription factor of KCNJ2 that encodes Kir2.1. Whether valsartan represses CK2 activation to ameliorate IK1 remodeling following MI remains unclear. Methods: Wistar rats suffering from MI received either valsartan or saline for 7days. The protein levels of CK2 and Kir2.1 were each detected via a Western blot analysis. The mRNA levels of CK2 and Kir2.1 were each examined via quantitative real-time PCR. Results: CK2 expression was higher at the infarct border; and was accompanied by a depressed IK1/Kir2.1 protein level. Additionally, CK2 overexpression suppressed KCNJ2/Kir2.1 expression. By contrast, CK2 inhibition enhanced KCNJ2/Kir2.1 expression, establishing that CK2 regulates KCNJ2 expression. Among the rats suffering from MI, valsartan reduced CK2 expression and increased Kir2.1 expression compared with the rats that received saline treatment. In vitro, hypoxia increased CK2 expression and valsartan inhibited CK2 expression. The over-expression of CK2 in cells treated with valsartan abrogated its beneficial effect on KCNJ2/Kir2.1. Conclusions: AT1 receptor antagonist valsartan reduces CK2 activation, increases Kir2.1 expression and thereby ameliorates IK1 remodeling after MI in the rat model. The Author(s), 2015 Myocardial infarction nationallicence CK2 nationallicence Kir2.1 nationallicence Valsartan nationallicence Rat nationallicence Li Xinran School of Medicine, Shandong University, Ji'nan, Shandong, China aut Hu Hesheng Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Wang Ye Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Xue Mei Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Li Xiaolu Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Cheng Wenjuan Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Xuan Yongli School of Medicine, Shandong University, Ji'nan, Shandong, China aut Yin Jie School of Medicine, Shandong University, Ji'nan, Shandong, China aut Yang Na School of Medicine, Shandong University, Ji'nan, Shandong, China aut Yan Suhua Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 209-218 0920-3206 29:3<209 2015 29 10557 https://doi.org/10.1007/s10557-015-6598-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6598-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Xinran School of Medicine, Shandong University, Ji'nan, Shandong, China aut NATIONALLICENCE 700 1- Hu Hesheng Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 700 1- Wang Ye Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 700 1- Xue Mei Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 700 1- Li Xiaolu Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 700 1- Cheng Wenjuan Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 700 1- Xuan Yongli School of Medicine, Shandong University, Ji'nan, Shandong, China aut NATIONALLICENCE 700 1- Yin Jie School of Medicine, Shandong University, Ji'nan, Shandong, China aut NATIONALLICENCE 700 1- Yang Na School of Medicine, Shandong University, Ji'nan, Shandong, China aut NATIONALLICENCE 700 1- Yan Suhua Department of Cardiology, Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, 250014, Jinan, Shandong Province, China aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 209-218 0920-3206 29:3<209 2015 29 10557