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

Kuan Chieh Wang, Po Sheng Chen, Ting Hsing Chao, Chawn Yau Luo, Hsing Chun Chung, Shih Ya Tseng, Ting Yu Huang, Ying Li Lin, Guey Yueh Shi, Hua Lin Wu, Yi Heng Li

研究成果: Article

摘要

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-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/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.

原文English
頁(從 - 到)54-63
頁數10
期刊Atherosclerosis
287
DOIs
出版狀態Published - 2019 八月

指紋

Thrombomodulin
Neointima
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Membrane
Phenotype
Ligation
Transgenic Mice
Vascular System Injuries
Carotid Arteries
Anticoagulants
Cultured Cells
Endothelial Cells
Arteries
Tumor Necrosis Factor-alpha
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

引用此文

Wang, Kuan Chieh ; 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. / The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation. 於: Atherosclerosis. 2019 ; 卷 287. 頁 54-63.
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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-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/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.",
author = "Wang, {Kuan Chieh} and Chen, {Po Sheng} and Chao, {Ting Hsing} and Luo, {Chawn Yau} and Chung, {Hsing Chun} and Tseng, {Shih Ya} and Huang, {Ting Yu} and Lin, {Ying Li} and Shi, {Guey Yueh} and Wu, {Hua Lin} and Li, {Yi Heng}",
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The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation. / Wang, Kuan Chieh; 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.

於: Atherosclerosis, 卷 287, 08.2019, p. 54-63.

研究成果: Article

TY - JOUR

T1 - The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation

AU - Wang, Kuan Chieh

AU - Chen, Po Sheng

AU - Chao, Ting Hsing

AU - Luo, Chawn Yau

AU - Chung, Hsing Chun

AU - Tseng, Shih Ya

AU - Huang, Ting Yu

AU - Lin, Ying Li

AU - Shi, Guey Yueh

AU - Wu, Hua Lin

AU - Li, Yi Heng

PY - 2019/8

Y1 - 2019/8

N2 - 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-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/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.

AB - 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-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/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.

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