Role of CaMKII in Ang-II-dependent small artery remodeling.

Role of CaMKII in Ang-II-dependent small artery remodeling.
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CaMKII在Ang-II依赖性小动脉重塑中的作用

DOI:
10.1016/j.vph.2016.09.007
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发表时间:
2016-12
影响因子:
4
通讯作者:
Grumbach, Isabella M.
Grumbach, Isabella M.
中科院分区:
医学2区
文献类型:
--
作者:
Prasad, Anand M.;Ketsawatsomkron, Pimonrat;Nuno, Daniel W.;Koval, Olha M.;Dibbern, Megan E.;Venema, Ashlee N.;Sigmund, Curt D.;Lamping, Kathryn G.;Grumbach, Isabella M.

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血管紧张素II(Ang-II)是血管重塑的公认介质。多功能钙-钙调蛋白依赖性激酶II(CaMKII)被Ang-II激活,并在体外培养的平滑肌细胞中调节Erk 1/2和Akt依赖性信号传导。其在体内Ang-II依赖性血管重塑中的作用远未被定义。使用一个模型的转基因CaMKII抑制选择性平滑肌细胞,我们发现,CaMKII抑制夸大重塑后,慢性血管紧张素II治疗和激动剂依赖性血管收缩二级肠系膜动脉。这些发现与平滑肌结构蛋白的mRNA和蛋白表达增加有关。作为一个潜在的机制,CaMKII降低血清反应因子依赖的转录活性。总之,我们的研究结果确定CaMKII作为血管紧张素II型高血压中平滑肌功能的重要调节剂。
Angiotensin-II (Ang-II) is a well-established mediator of vascular remodeling. The multifunctional calcium-calmodulin-dependent kinase II (CaMKII) is activated by Ang-II and regulates Erk1/2 and Akt-dependent signaling in cultured smooth muscle cells in vitro. Its role in Ang-II-dependent vascular remodeling in vivo is far less defined. Using a model of transgenic CaMKII inhibition selectively in smooth muscle cells, we found that CaMKII inhibition exaggerated remodeling after chronic Ang-II treatment and agonist-dependent vasoconstriction in second-order mesenteric arteries. These findings were associated with increased mRNA and protein expression of smooth muscle structural proteins. As a potential mechanism, CaMKII reduced serum response factor-dependent transcriptional activity. In summary, our findings identify CaMKII as an important regulator of smooth muscle function in Ang-II hypertension in vivo.
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