Activation of apoptosis signal-regulating kinase 1 in injured artery and its critical role in neointimal hyperplasia
- PMID: 14638553
- DOI: 10.1161/01.CIR.0000096486.01652.FC
Activation of apoptosis signal-regulating kinase 1 in injured artery and its critical role in neointimal hyperplasia
Abstract
Background: Apoptosis signal-regulating kinase 1 (ASK1), recently identified as one of the mitogen-activated protein kinase kinase kinases, is activated by various extracellular stimuli and involved in a variety of cellular function. Therefore, we first examined the role of ASK1 in vascular remodeling.
Methods and results: We used rat balloon injury model and cultured vascular smooth muscle cells (VSMCs). Arterial ASK1 activity was rapidly and dramatically increased after balloon injury. To specifically inhibit endogenous ASK1 activation, dominant-negative mutant of ASK1 (DN-ASK1) was transfected into rat carotid artery before balloon injury. Gene transfer of DN-ASK1 significantly prevented neointimal formation at 14 days after injury. Bromodeoxyuridine labeling index at 7 days after injury showed that DN-ASK1 remarkably suppressed VSMC proliferation in both the intima and the media. We also examined the role of ASK1 in cultured rat VSMCs. Infection with DN-ASK1 significantly attenuated serum-induced VSMC proliferation and migration. We also compared neointimal formation after cuff placement around the femoral artery between mice deficient in ASK1 (ASK1-/- mice) and wild-type (WT) mice. Neointimal formation at 28 days after cuff injury in ASK1-/- mice was significantly attenuated compared with WT mice. Furthermore, we compared the proliferation and migration of VSMCs isolated from ASK1-/- mice with WT mice. Both proliferation and migration of VSMCs from ASK1-/- mice were significantly attenuated compared with VSMCs from WT mice.
Conclusions: ASK1 activation plays the key role in vascular intimal hyperplasia. ASK1 may provide the basis for the development of new therapeutic strategy for vascular diseases.
Similar articles
-
Inhibition of vascular smooth muscle cell proliferation and neointimal formation in injured arteries by a novel, oral mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor.Circulation. 2004 Nov 23;110(21):3367-71. doi: 10.1161/01.CIR.0000147773.86866.CD. Epub 2004 Nov 1. Circulation. 2004. PMID: 15520324
-
Gene transfer of dominant-negative mutants of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase prevents neointimal formation in balloon-injured rat artery.Circ Res. 2001 Jun 8;88(11):1120-6. doi: 10.1161/hh1101.091267. Circ Res. 2001. PMID: 11397777
-
Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries.Cardiovasc Res. 2005 Nov 1;68(2):249-58. doi: 10.1016/j.cardiores.2005.06.016. Epub 2005 Jul 21. Cardiovasc Res. 2005. PMID: 16039635
-
ADAMTS-7, a novel proteolytic culprit in vascular remodeling.Sheng Li Xue Bao. 2010 Aug 25;62(4):285-94. Sheng Li Xue Bao. 2010. PMID: 20717629 Review.
-
Critical and diverse in vivo roles of apoptosis signal-regulating kinase 1 in animal models of atherosclerosis and cholestatic liver injury.Histol Histopathol. 2017 May;32(5):433-444. doi: 10.14670/HH-11-840. Epub 2016 Nov 9. Histol Histopathol. 2017. PMID: 27826954 Review.
Cited by
-
The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease.Cells. 2019 Nov 4;8(11):1383. doi: 10.3390/cells8111383. Cells. 2019. PMID: 31689891 Free PMC article. Review.
-
ASK family in cardiovascular biology and medicine.Adv Biol Regul. 2017 Dec;66:54-62. doi: 10.1016/j.jbior.2017.10.011. Epub 2017 Oct 24. Adv Biol Regul. 2017. PMID: 29107568 Free PMC article. Review.
-
Apoptosis signal-regulating kinase 1 exhibits oncogenic activity in pancreatic cancer.Oncotarget. 2016 Nov 15;7(46):75155-75164. doi: 10.18632/oncotarget.12090. Oncotarget. 2016. PMID: 27655673 Free PMC article.
-
In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice.Transgenic Res. 2007 Jun;16(3):281-314. doi: 10.1007/s11248-006-9052-0. Epub 2007 Jan 12. Transgenic Res. 2007. PMID: 17219248 Review.
-
ASK1 inhibition: a therapeutic strategy with multi-system benefits.J Mol Med (Berl). 2020 Mar;98(3):335-348. doi: 10.1007/s00109-020-01878-y. Epub 2020 Feb 14. J Mol Med (Berl). 2020. PMID: 32060587 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous