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

详细信息    查看全文

• 作者：Anand M. Prasad^a ; Pimonrat Ketsawatsomkron^b ; Daniel W. Nuno^a ; ^b ; Olha M. Koval^a ; Megan E. Dibbern^a ; Ashlee N. Venema^a ; Curt D. Sigmund^a ; ^b ; ^c ; Kathryn G. Lamping^a ; ^b ; ^d ; Isabella M. Grumbach^a ; ^d ; ^{isabella-grumbach@uiowa.edu}
• 关键词：CaMKII ; Ang-II ; Remodeling ; Smooth muscle
• 刊名：Vascular Pharmacology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：172-179
• 全文大小：1040 K
• 卷排序：87

文摘

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.