Journal article
Deletion of Methionine Sulfoxide Reductase A Does Not Affect Atherothrombosis but Promotes Neointimal Hyperplasia and Extracellular Signal-Regulated Kinase 1/2 Signaling
Arteriosclerosis, thrombosis, and vascular biology, Vol.35(12), pp.2594-2604
12/2015
DOI: 10.1161/ATVBAHA.115.305857
PMCID: PMC4662651
PMID: 26449752
Abstract
Emerging evidence suggests that methionine oxidation can directly affect protein function and may be linked to cardiovascular disease. The objective of this study was to define the role of the methionine sulfoxide reductase A (MsrA) in models of vascular disease and identify its signaling pathways.
MsrA was readily identified in all layers of the vascular wall in human and murine arteries. Deletion of the MsrA gene did not affect atherosclerotic lesion area in apolipoprotein E-deficient mice and had no significant effect on susceptibility to experimental thrombosis after photochemical injury. In contrast, the neointimal area after vascular injury caused by complete ligation of the common carotid artery was significantly greater in MsrA-deficient than in control mice. In aortic vascular smooth muscle cells lacking MsrA, cell proliferation was significantly increased because of accelerated G1/S transition. In parallel, cyclin D1 protein and cdk4/cyclin D1 complex formation and activity were increased in MsrA-deficient vascular smooth muscle cell, leading to enhanced retinoblastoma protein phosphorylation and transcription of E2F. Finally, MsrA-deficient vascular smooth muscle cell exhibited greater activation of extracellular signal-regulated kinase 1/2 that was caused by increased activity of the Ras/Raf/mitogen-activated protein kinase signaling pathway.
Our findings implicate MsrA as a negative regulator of vascular smooth muscle cell proliferation and neointimal hyperplasia after vascular injury through control of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling pathway.
Details
- Title: Subtitle
- Deletion of Methionine Sulfoxide Reductase A Does Not Affect Atherothrombosis but Promotes Neointimal Hyperplasia and Extracellular Signal-Regulated Kinase 1/2 Signaling
- Creators
- Paula J Klutho - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaSteven M Pennington - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaJason A Scott - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaKatina M Wilson - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaSean X Gu - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaPrakash Doddapattar - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaLitao Xie - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaAshlee N Venema - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaLinda J Zhu - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaAnil K Chauhan - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaSteven R Lentz - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of IowaIsabella M Grumbach - From the Department of Internal Medicine (P.J.K., S.M.P., J.A.S., K.M.W., S.X.G., P.D., L.X., A.N.V., L.J.Z., A.K.C., S.R.L.) and the Iowa City VA Healthcare System (I.M.G.), University of Iowa. isabella-grumbach@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.35(12), pp.2594-2604
- DOI
- 10.1161/ATVBAHA.115.305857
- PMID
- 26449752
- PMCID
- PMC4662651
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Grant note
- R01 HL118742 / NHLBI NIH HHS T32 HL007121 / NHLBI NIH HHS R01 HL108932 / NHLBI NIH HHS R01HL118246 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS R01HL118742 / NHLBI NIH HHS I01 BX000163 / BLRD VA R01 HL063943 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS R01 HL118246 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Radiation Oncology; Chemistry; Internal Medicine
- Record Identifier
- 9984094553702771
Metrics
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