Review
Biochemistry & Molecular Biology
Machteld Sillen, Paul J. Declerck
Summary: TAFI, a proenzyme, is converted to a potent attenuator of the fibrinolytic system upon activation by thrombin, plasmin, or the thrombin/thrombomodulin complex. The development of molecules antagonizing TAFI function has gained much interest in the field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Arnaud-Pierre Schaffner, Patricia Sansilvestri-Morel, Nicole Despaux, Elisabeth Ruano, Thierry Persigand, Alain Rupin, Philippe Mennecier, Marie-Odile Vallez, Eric Raimbaud, Patrice Desos, Philippe Gloanec
Summary: Novel inhibitors targeting TAFIa designed in this paper show promising activity in thrombosis models, suggesting their potential for use in treating thrombotic diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Karen Claesen, Joachim C. Mertens, Dorien Leenaerts, Dirk Hendriks
Summary: This paper provides an overview of Procarboxypeptidase U and related research, highlighting the novel concept of using CPU inhibitors as profibrinolytic agents, as well as the potential significance and clinical applications of CPU in thromboembolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Thomas Vanassche, Rachel P. Rosovsky, Fares Moustafa, Harry R. Buller, Annelise Segers, Indu Patel, Minggao Shi, Naoki Miyoshi, Venkatesh Mani, Zahi Fayad, Dominique Stephan, Jeannot Schmidt, Michael A. Grosso, Victor F. Tapson, Peter Verhamme, M. Huisman
Summary: This study evaluated the tolerability and efficacy of adding DS-1040 in patients with intermediate-risk PE. The results showed that adding DS-1040 did not increase bleeding risk, but also did not improve thrombus resolution or right ventricular dilation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Erasmia Rouka, Sotirios G. Zarogiannis, Chrissi Hatzoglou, Konstantinos I. Gourgoulianis, Foteini Malli
Summary: This study focuses on the prediction and functional enrichment analysis of the TAFI interaction network and the microRNAs targeting the members of this network. It identifies the complement and coagulation cascades as well as neutrophil extracellular trap formation as pathways related to TAFI-related thrombosis and identifies important diseases such as cancer, stroke, and intracranial aneurysm associated with the identified microRNAs.
Article
Biochemical Research Methods
Jun X. Wheeler, Craig Thelwell, Peter Rigsby, Gail Whiting
Summary: In this study, a quantitative mass spectrometry method was established for measuring TAFI in human plasma. Traceability was achieved by using calibrators consisting of blank plasma spiked with a known amount of purified TAFI. This method enabled reliable and accurate measurement of TAFI concentration in plasma and demonstrated its applicability for assigning a common reference standard.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Kanako Yoshida, Tetsuji Takabayashi, Yoshimasa Imoto, Masafumi Sakashita, Yukinori Kato, Norihiko Narita, Shigeharu Fujieda
Summary: This study found that serum TAFI levels significantly increased after SLIT treatment, showing a significant negative correlation with C3a levels, and inhibited mast cell degranulation and chemokine expression in fibroblasts.
Article
Hematology
Patricia Sansilvestri-Morel, Alain Rupin, Arnaud-Pierre Schaffner, Florence Bertin, Philippe Mennecier, Isabelle Lapret, Paul J. Declerck, Philippe Baumy, Marie-Odile Vallez, Florence Petit-Dop, Isabelle Tupinon-Mathieu, Philippe Delerive
Summary: The new TAFIa inhibitor S62798 has been found to enhance fibrinolysis in both in vitro and in vivo studies, with minimal risk of bleeding. This inhibitor has the potential to be a therapeutic option for treating pulmonary embolism in combination with anticoagulants.
THROMBOSIS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Hanyu Liang, Zhongzhu Hong, Shihua Li, Xiaorong Song, Da Zhang, Qiushui Chen, Juan Li, Huanghao Yang
Summary: Thrombin-activatable scintillating nanoprobes have been developed for background-free X-ray-excited luminescence (XEL) imaging of early thrombosis in vivo, by designing bright XEL-emitting lanthanide-doped scintillator nanocrystals with dye labeled-peptide modification. The strategy achieves high-efficiency XEL imaging of early thrombosis based on in situ elevated thrombin levels, demonstrating a novel paradigm for timely thrombosis imaging and providing a readily tailorable platform for sensitive in vivo deep-tissue imaging.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Critical Care Medicine
Julia R. Coleman, Ernest E. Moore, Marguerite R. Kelher, Kenneth Jones, Mitchell J. Cohen, Anirban Banerjee, Christopher C. Silliman
Summary: This study revealed that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a major role in fibrinolysis shutdown after trauma-induced coagulopathy.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2023)
Article
Clinical Neurology
Joachim C. Mertens, Vanessa Blanc-Guillemaud, Karen Claesen, Pere Cardona, Dirk Hendriks, Benoit Tyl, Carlos A. Molina
Summary: The study evaluated the kinetics of CPU during ischemic stroke treatment, revealing rapid activation and deactivation of the CPU system following thrombolysis and thrombectomy, indicating that a CPU inhibitor would need to be administered during rtPA infusion and in the hours that follow.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Hematology
Ping Fang, Decheng Cai, Lijun Du, Fei Shen, Chengfang Zhang, Meijuan Li
Summary: The study suggests a protective role of the TAFI +1040C allele against recurrent spontaneous abortion, with a lower frequency of the C allele in RSA patients. The +1040CT genotype was significantly higher and the +1040CC genotype was significantly lower in RSA patients compared to controls.
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
(2021)
Article
Pharmacology & Pharmacy
Sjoukje van Der Hoek, Antoon T. M. Willemsen, Ton Visser, Andre Heeres, Douwe J. Mulder, Reinoud P. H. Bokkers, Riemer H. J. A. Slart, Philip H. Elsinga, Hiddo J. L. Heerspink, Jasper Stevens
Summary: SGLT2 inhibitors reduce cardiovascular and kidney risks, but there is individual variation in response. The use of [F-18]canagliflozin PET imaging in this study helped determine the association between clinical canagliflozin doses and SGLT2 occupancy.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Immunology
Xiaojuan Zhang, Xin Xu, Jia Chen, Guan Wang, Qiang Li, Min Li, Jianzhong Lu
Summary: HHT-9041P1, a selective JAK1 inhibitor, has shown high selectivity and preclinical efficacy in vitro and in vivo experiments, making it a potential candidate for the treatment of RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Karen Claesen, Lynn Roth, Joachim C. Mertens, Karlijn Hermans, Yani Sim, Dirk Hendriks
Summary: Studies indicate that statins can reduce levels of procarboxypeptidase U in a cardiovascular disease model mouse, independent of their cholesterol-lowering effects, demonstrating a pleiotropic effect of statin treatment.