TY - JOUR
T1 - Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study
AU - Cheung, Y. Whitney
AU - Bouman, Annemieke C.
AU - Castoldi, Elisabetta
AU - Wielders, Simone J.
AU - Spronk, Henri M. H.
AU - ten Cate, Hugo
AU - Hoek - ten Cate, Arina
AU - ten Wolde, Marije
PY - 2016/4
Y1 - 2016/4
N2 - Objective: Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence. Methods: Patients with a history of DVT with PTS (cases, n = 30) and without PTS after minimal 24 months follow-up (controls, n= 30) were selected. Healthy individuals (HI, n= 29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the Delta Ct method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes. Results: The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p = 0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p=0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p <0.01). Conclusion: No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT.
AB - Objective: Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence. Methods: Patients with a history of DVT with PTS (cases, n = 30) and without PTS after minimal 24 months follow-up (controls, n= 30) were selected. Healthy individuals (HI, n= 29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the Delta Ct method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes. Results: The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p = 0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p=0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p <0.01). Conclusion: No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT.
KW - Toll-like 9 receptor
KW - Deep vein thrombosis
KW - Post-thrombotic syndrome
KW - Residual thrombosis
KW - Recurrent deep venous thrombosis
U2 - 10.1016/j.thromres.2016.02.025
DO - 10.1016/j.thromres.2016.02.025
M3 - Article
C2 - 26938157
SN - 0049-3848
VL - 140
SP - 106
EP - 109
JO - Thrombosis Research
JF - Thrombosis Research
ER -