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Valsartan Upregulates Kir2.1 in Rats Suffering from Myocardial Infarction via Casein Kinase 2.

Li X, Hu H, Wang Y, Xue M, Li X, Cheng W, Xuan Y, Yin J, Yang N, Yan S - Cardiovasc Drugs Ther (2015)

Bottom Line: 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.AT1 receptor antagonist valsartan reduces CK2 activation, increases Kir2.1 expression and thereby ameliorates IK1 remodeling after MI in the rat model.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.

ABSTRACT

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 7 days. 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.

No MeSH data available.


Related in: MedlinePlus

The upregulation of CK2 and the downregulation of KCNJ2/Kir2.1 in MI rats. A qPCR analysis and a Western blot analysis demonstrating the significant upregulation of CK2 and the downregulation of Kir2.1 in ventricular myocytes at a ventricular infarct border in a rat MI model. Similar results showing in noninfarcted LVFW of MI rats. *P < 0.05 vs. control; n = 10/group. Values are expressed as the means ± SDs
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Fig2: The upregulation of CK2 and the downregulation of KCNJ2/Kir2.1 in MI rats. A qPCR analysis and a Western blot analysis demonstrating the significant upregulation of CK2 and the downregulation of Kir2.1 in ventricular myocytes at a ventricular infarct border in a rat MI model. Similar results showing in noninfarcted LVFW of MI rats. *P < 0.05 vs. control; n = 10/group. Values are expressed as the means ± SDs

Mentions: In an effort to determine the role of CK2 in acute myocardial infarction (AMI), we found that CK2 was significantly upregulated. Consistent with the findings of previous studies [27–29], we found that Kir2.1 protein expression was downregulated in MI rats (Fig. 2). Besides, the KCNJ2 mRNA expression was also downregulated during the healing phase after AMI, suggesting that the regulation of Kir2.1 protein at 7 days after MI is not only on translation but also on mRNA level. These results are consistent with the hypothesis that CK2 contributes to KCNJ2 dysregulation in the setting of MI, a possibility that we elected to test directly.Fig. 2


Valsartan Upregulates Kir2.1 in Rats Suffering from Myocardial Infarction via Casein Kinase 2.

Li X, Hu H, Wang Y, Xue M, Li X, Cheng W, Xuan Y, Yin J, Yang N, Yan S - Cardiovasc Drugs Ther (2015)

The upregulation of CK2 and the downregulation of KCNJ2/Kir2.1 in MI rats. A qPCR analysis and a Western blot analysis demonstrating the significant upregulation of CK2 and the downregulation of Kir2.1 in ventricular myocytes at a ventricular infarct border in a rat MI model. Similar results showing in noninfarcted LVFW of MI rats. *P < 0.05 vs. control; n = 10/group. Values are expressed as the means ± SDs
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4522035&req=5

Fig2: The upregulation of CK2 and the downregulation of KCNJ2/Kir2.1 in MI rats. A qPCR analysis and a Western blot analysis demonstrating the significant upregulation of CK2 and the downregulation of Kir2.1 in ventricular myocytes at a ventricular infarct border in a rat MI model. Similar results showing in noninfarcted LVFW of MI rats. *P < 0.05 vs. control; n = 10/group. Values are expressed as the means ± SDs
Mentions: In an effort to determine the role of CK2 in acute myocardial infarction (AMI), we found that CK2 was significantly upregulated. Consistent with the findings of previous studies [27–29], we found that Kir2.1 protein expression was downregulated in MI rats (Fig. 2). Besides, the KCNJ2 mRNA expression was also downregulated during the healing phase after AMI, suggesting that the regulation of Kir2.1 protein at 7 days after MI is not only on translation but also on mRNA level. These results are consistent with the hypothesis that CK2 contributes to KCNJ2 dysregulation in the setting of MI, a possibility that we elected to test directly.Fig. 2

Bottom Line: 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.AT1 receptor antagonist valsartan reduces CK2 activation, increases Kir2.1 expression and thereby ameliorates IK1 remodeling after MI in the rat model.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.

ABSTRACT

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 7 days. 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.

No MeSH data available.


Related in: MedlinePlus