Oxidative activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates vascular smooth muscle migration and apoptosis

Linda J Zhu; Paula J Klutho; Jason A Scott; Litao Xie; Elizabeth D Luczak; Megan E Dibbern; Anand M Prasad; Omar A Jaffer; Ashlee N Venema; Emily K Nguyen; Xiaoqun Guan; Mark E Anderson; Isabella M Grumbach

doi:10.1016/j.vph.2014.01.001

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Oxidative activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates vascular smooth muscle migration and apoptosis

Journal article

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Oxidative activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates vascular smooth muscle migration and apoptosis

Linda J Zhu, Paula J Klutho, Jason A Scott, Litao Xie, Elizabeth D Luczak, Megan E Dibbern, Anand M Prasad, Omar A Jaffer, Ashlee N Venema, Emily K Nguyen, …

Vascular pharmacology, Vol.60(2), pp.75-83

02/2014

DOI: 10.1016/j.vph.2014.01.001

PMCID: PMC3955051

PMID: 24418021

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Abstract

Activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and reactive oxygen species (ROS) promote neointimal hyperplasia after vascular injury. CaMKII can be directly activated by ROS through oxidation. In this study, we determined whether abolishing the oxidative activation site of CaMKII alters vascular smooth muscle cell (VCMC) proliferation, migration and apoptosis in vitro and neointimal formation in vivo. VSMC isolated from a knock-in mouse with oxidation-resistant CaMKIIδ (CaMKII M2V) displayed similar proliferation but decreased migration and apoptosis. Surprisingly, ROS production and expression of the NADPH oxidase subunits p47 and p22 were decreased in M2V VSMC, whereas superoxide dismutase 2 protein expression was upregulated. In vivo, after carotid artery ligation, no differences in neointimal size or remodeling were observed. In contrast to VSMC, CaMKII expression and autonomous activity were significantly higher in M2V compared to WT carotid arteries, suggesting that an autoregulatory mechanism determines CaMKII activity in vivo. Our findings demonstrate that preventing oxidative activation of CaMKII decreases migration and apoptosis in vitro and suggest that CaMKII regulates ROS production. Our study presents novel evidence that CaMKII expression in vivo is regulated by a negative feedback loop following oxidative activation. [Display omitted]

Reactive oxygen species

CaMKII

Proliferation

Migration

Apoptosis

Details

Title: Subtitle: Oxidative activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates vascular smooth muscle migration and apoptosis
Creators: Linda J Zhu - Department of Medicine, Iowa City, IA, United States
Paula J Klutho - Department of Medicine, Iowa City, IA, United States
Jason A Scott - Department of Medicine, Iowa City, IA, United States
Litao Xie - Department of Medicine, Iowa City, IA, United States
Elizabeth D Luczak - Department of Medicine, Iowa City, IA, United States
Megan E Dibbern - Department of Medicine, Iowa City, IA, United States
Anand M Prasad - Department of Medicine, Iowa City, IA, United States
Omar A Jaffer - Department of Medicine, Iowa City, IA, United States
Ashlee N Venema - Department of Medicine, Iowa City, IA, United States
Emily K Nguyen - Department of Medicine, Iowa City, IA, United States
Xiaoqun Guan - Department of Medicine, Iowa City, IA, United States
Mark E Anderson - Department of Medicine, Iowa City, IA, United States
Isabella M Grumbach - Department of Medicine, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Vascular pharmacology, Vol.60(2), pp.75-83
DOI: 10.1016/j.vph.2014.01.001
PMID: 24418021
PMCID: PMC3955051
NLM abbreviation: Vascul Pharmacol
ISSN: 1537-1891
eISSN: 1879-3649
Publisher: Elsevier Inc
Language: English
Date published: 02/2014
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Internal Medicine
Record Identifier: 9984094396202771

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