The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation

doi:10.1016/j.atherosclerosis.2019.05.019

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/32620

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/32620

Title:	The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation
Authors:	Kuan-Chieh Wang(王冠傑) Chen, Po-Sheng Chao, Ting-Hsing Luo, Chawn-Yau Chung, Hsing-Chun Tseng, Shih-Ya Huang, Ting-Yu Lin, Ying-Li Shi, Guey-Yueh Wu, Hua-Lin Li, Yi-Heng
Contributors:	Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol Chia Nan Univ Pharm & Sci, Dept Pharm Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Inst Clin Med, Coll Med Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Surg, Coll Med
Keywords:	Neointima Smooth muscle cell Thrombomodulin
Date:	2019-08
Issue Date:	2020-07-29 13:52:26 (UTC+8)
Publisher:	ELSEVIER IRELAND LTD
Abstract:	Background and aims: Thrombomodulin (TM) is an endothelial cell membrane-bound anticoagulant protein expressed in normal arteries. After vascular injury, medial and neointimal smooth muscle cells (SMCs) exhibit large amounts of TM. The purpose of this study was to investigate the physiological significance of vascular SMC-bound TM. Methods: The morphology, expression of phenotype markers and cell behaviors of cultured aortic SMCs after knockdown of TM were observed. Transgenic mice with SMC-specific TM deletion were generated, and carotid neointima formation was induced by carotid ligation. Results: Cultured human aortic SMCs displayed a synthetic phenotype with a rhomboid-shaped morphology and expressed TM. TM knockdown induced a spindle-shaped change in morphology with an increased expression of contractile phenotype marker and decreased expression of synthetic phenotype marker. TM knockdown not only attenuated the proliferation of SMCs but also reduced tumor necrosis factor-alpha-induced nuclear factor-kappa B activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cre(tg)/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cre(tg)/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cre(tg)/TMflox/flox mice at 4 weeks after ligation. Conclusions: Our results indicate that vascular SMC-bound TM plays a role in changes of the SMC phenotype. It also influences SMC cell behavior and injury-induced neointima formation.
Relation:	Atherosclerosis, v.287, pp.54-63
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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