Thrombin-activatable fibrinolysis inhibitor in chronic thromboembolic pulmonary hypertension

Nobuhiro Yaoita, Kimio Satoh, Taijyu Satoh, Koichiro Sugimura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Masanobu Miura, Satoshi Miyata, Takeshi Kawamura, Hisanori Horiuchi, Yoshihiro Fukumoto, Hiroaki Shimokawa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective - The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis. 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. Approach and Results - We enrolled 68 consecutive patients undergoing right heart catheterization in our hospital, including those with CTEPH (n=27), those with pulmonary arterial hypertension (n=22), and controls (non-pulmonary hypertension, n=19). Whole blood clot lysis assay showed that the extent of clot remaining after 4 hours was significantly higher in CTEPH compared with pulmonary arterial hypertension or controls (41.9 versus 26.5 and 24.6%, both P<0.01). Moreover, plasma levels of TAFI were significantly higher in CTEPH than in pulmonary arterial hypertension or controls (19.4±4.2 versus 16.1±4.5 or 16.3±3.3 μg/mL, both P<0.05), which remained unchanged even after hemodynamic improvement by percutaneous transluminal pulmonary angioplasty. Furthermore, the extent of clot remaining after 4 hours was significantly improved with CPI-2KR (an inhibitor of activated TAFI) or prostaglandin E 1 (an inhibitor of activation of platelets). Importantly, plasma levels of TAFI were significantly correlated with the extent of clot remaining after 4 hours. In addition, the extent of clot remaining after 4 hours was improved with an activated TAFI inhibitor. Conclusions - These results indicate that plasma levels of TAFI are elevated in patients with CTEPH and are correlated with resistance to clot lysis in those patients.

Original languageEnglish
Pages (from-to)1293-1301
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • angioplasty
  • fibrinolysis
  • hemodynamics
  • plasma
  • pulmonary hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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