2016.05.13 Press Release

Novel pathogenesis in chronic thromboembolic pulmonary hypertension: Involvement of thrombin-activatable fibrinolysis inhibitor

A research group led by Professor Hiroaki Shimokawa of the Department of Cardiovascular Medicine in Tohoku University Graduate School of Medicine has reported that thrombin-activatable fibrinolysis inhibitor as a key factor of Chronic thromboembolic pulmonary hypertension.

• The capacity of fibrinolysis in CTEPH was impaired and the plasma levels of TAFI was high in CTEPH patients.
• SNPs which increased the plasma levels of TAFI was found in CTEPH patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the distinct disease entities of pulmonary hypertension (PH), characterized by obstruction of major pulmonary artery by organized thrombus and pulmonary vascular remodeling. CTEPH leads to increased pulmonary vascular resistance, progressive pulmonary hypertension and right heart failure to death. There are a few reports regarding the association between CTEPH and coagulation abnormality. Thus, it remains to be examined whether fibrinolysis capacity is impaired in CTEPH and if so, what molecular mechanism(s) is involved.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma carboxypeptidase inhibitor which inhibits fibrinolysis. TAFI is activated by thrombin, thrombin/thrombomodulin complex, plasmin and activated platelets, while activated form of TAFI (aTAFI) removes the C-terminal lysines from fibrin and reduces the binding of tPA and plasmin to the fibrin. It remains to be elucidated whether TAFI is directly involved in the pathogenesis of CTEPH. We examined potential involvement of TAFI in the pathogenesis of CTEPH in humans. We showed that the fibrinolysis was impaired and the plasma levels of TAFI were high in in CTEPH patients. After the treatment of CTEPH, the plasma levels of TAFI did not change. Prevalence of single nucleotide polymorphisms (SNPs) which increased the plasma levels of TAFI was higher in CTEPH patients. These results indicate that the plasma levels of TAFI was high congenitally in CTEPH patients. The impairment of fibrinolysis in CTEPH patients was improved with the inhibition of TAFI. These results might contribute to development of the early diagnosis of CTEPH and novel therapy of CTEPH.

The research result was published in the Arteriosclerosis, Thrombosis, and Vascular Biology on April 21, 2016. The paper’s title is “Thrombin-activatable Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension”

(About the research)
Professor Hiroaki Shimokawa
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
TEL: +81-22-717-7152
E-mail: shimo* (Replace * with @)

(Public Relations)
Lecturer Hitoshi Inada
Public Relations Office of Tohoku University Graduate School of Medicine
TEL: +81-22-717-7891 FAX: +81-22-717-8187
E-mail: pr-office* (Replace * with @)