Remodeling of carotid arteries is associated with increased expression of thrombomodulin in a mouse transverse aortic constriction model

Yi-Heng Li; Chung-Yu Hsieh; Danny Ling Wang; Hsing-Chun Chung; Shu-Lin Liu; Ting-Hsing Chao; Guey-Yueh Shi; Hua-Lin Wu

doi:10.1160/TH06-12-0690

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 658-664
DOI: 10.1160/TH06-12-0690

Animal Models

Schattauer GmbH

Remodeling of carotid arteries is associated with increased expression of thrombomodulin in a mouse transverse aortic constriction model

Yi-Heng Li

¹Department of Internal Medicine

²Cardiovascular Research Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Chung-Yu Hsieh

³Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

,

Danny Ling Wang

³Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

,

Hsing-Chun Chung

¹Department of Internal Medicine

²Cardiovascular Research Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Shu-Lin Liu

⁴Department of Biochemistry and Molecular Biology

⁵Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Ting-Hsing Chao

¹Department of Internal Medicine

²Cardiovascular Research Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Guey-Yueh Shi

²Cardiovascular Research Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

⁴Department of Biochemistry and Molecular Biology

,

Hua-Lin Wu

²Cardiovascular Research Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

⁴Department of Biochemistry and Molecular Biology

› Author Affiliations

Abstract

Summary

Thrombomodulin (TM) is an endothelial glycoprotein that functions as a thrombin cofactor in the activation of protein C. Recent evidence has revealed that TM has unique effects on cellular proliferation, adhesion, and inflammation. We examined TM expression in the arterial remodeling process with different shear conditions. Quantitative real-time reverse transcription- PCR (Q-PCR) revealed that shear stress (25 dyne/cm² for 6 hours) induced a 2.6 ± 0.4 -fold increase inTM mRNA levels in endothelial cell culture. Adult FVB (Friend leukemia virus B strain) mice underwent transverse aortic constriction (TAC) between the right (RCA) and left carotid artery (LCA). Doppler (n = 8), morphometric (n = 8), and Q-PCR (n = 8 or 10) studies were performed on carotid arteries at different time points. The RCA lumen and media area increased. The LCA wall shear stress decreased after TAC. RCA wall shear stress increased at day 7 followed by a decrease to the baseline at day 28.TM mRNA level in the LCA was decreased by 61% at day 7 after TAC (0.39 ± 0.04; p<0.05 vs. baseline). It progressively returned to the baseline at day 14 (0.85 ± 0.12) and day 28 (1.48 ± 0.05; all p = NS). TM appeared in the media of the RCA;TM mRNA level in the RCA was increased by 11-fold at day 14 after TAC (11.0 ± 0.22) and progressively decreased at day 28 (5.34 ± 0.25, all p<0.05 vs. baseline). Our studies suggested that altered shear stress induced significantTM gene expression changes during the arterial remodeling process.

Keywords

Arterial remodeling - atherosclerosis - thrombomodulin

Full Text

References

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