title: Role of CaMKII in Ang-II-dependent small artery remodeling.
abstract: 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.
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States.
authors.forename: Anand M
authors.initials: AM
authors.lastname: Prasad
authors.affiliation: Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, United States.
authors.forename: Pimonrat
authors.initials: P
authors.lastname: Ketsawatsomkron
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States; Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, United States.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Nuno
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States.
authors.forename: Olha M
authors.initials: OM
authors.lastname: Koval
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Dibbern
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States.
authors.forename: Ashlee N
authors.initials: AN
authors.lastname: Venema
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States; Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, United States; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States.
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States; Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, United States; Iowa City VA Healthcare System, Iowa City, United States.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Lamping
authors.affiliation: Department of Medicine, Carver College, University of Iowa, Iowa City, United States; Iowa City VA Healthcare System, Iowa City, United States. Electronic address: isabella-grumbach@uiowa.edu.
authors.forename: Isabella M
authors.initials: IM
authors.lastname: Grumbach
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D000804:Angiotensin II; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Ang-II; CaMKII; Remodeling; Smooth muscle