Thrombomodulin Gene Polymorphism (C1418T) is Associated with the Development of Coronary Allograft Vasculopathy

Abstract

The first two authors contributed equal to this work Thrombomodulin (TM) is the endothelial cell membrane-bound anticoagulant protein cofactor in the thrombin-mediated activation of protein C. Previous evidence has been reported regarding the association between TM polymorphisms and coronary artery disease. Allograft rejection-mediated vasculopathy is the main cause of death at more than one year after heart transplantation. However, whether TM polymorphism is associated with allograft rejection is still unclear. We analyzed the TM gene polymorphism C1418T using allele-specific primers in a PCR assay in 60 patients who underwent heart transplantation. The retrospective clinical data were collected and tested for any correlations with the TM gene polymorphism. We separated the patients into 2 groups according to their TM genotype (group 1: CC genotype; group 2: cre-TT genotype). Additionally, we generated expression constructs (TM fulllength-Cl418 and TM fulllength-TI418) and performed in vitro studies to explore the correlation between the TM C1418T polymorphism and the migration of smooth muscle progenitor cells and monocytes, which may be involved in the development of vasculopathy. The results showed that the levels of CD68, C4d, PAS, and Masson staining in the CT/TT genotype group increased at year 1 and continued to increase throughout the 3 years. These levels were higher than those observed in the CC genotype group. The ISHLT-WF2004 grade ofthe CT/TT genotype group was significantly different from that of the CC genotype group at the same time point post-transplantation. The coronary allograft vasculopathy (CAY) score was significantly different between the CC and CT/TT genotype groups at 1 and 3 years post-transplantation. Our in vitro studies demonstrate that both smooth muscle progenitor cells and monocytic THP-l cells with either the CT-1418 or the TT-1418 TM genotype have higher migratory abilities than cells with the CC-1418 genotype. Our results support a significant association between the TM C1418T polymorphism and the development of CAY after heart transplantation in the short-to medium-term.

A Thrombomodulin Gene Polymorphism (C1418T) Is Associated with Early Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery with a Conventional Cardiopulmonary Bypass during Hospitalization

“…Additionally, the transgenic expression of human TM has anti-coagulant and anti-inflammatory effects, resulting in the protection of allografts [ 18 ]; plasma-soluble TM levels are elevated in patients who have undergone hemodialysis, while levels are significantly decreased after kidney transplantation. Recently, although we have previously demonstrated that the blood levels of TM are not associated with the occurrence of vasculopathy, a correlation between the TM C1418T polymorphism and the development of vasculopathy after heart transplantation was observed [ 36 ].…”

Determination of Polycyclic Aromatic Hydrocarbons (PAHs) in Ginkgo Biloba Extracts by HPLC with Fluorescence Detection

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Isolation and Purification of Ginkgo Flavonoids by High-Speed Counter-Current Chromatography

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