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

Abstract

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/cm(2) for 6 hours) induced a 2.6 +/- 0.4-fold increase in TM 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 significant TM gene expression changes during the arterial remodeling process.