Article
Hematology
Sujuan Li, Weili Wang, Lisha Lin, Lian Yang, Ying Cai, Xingzhi Yang, Taocui Zhang, Chuang Xiao, Hui Yan, Na Gao, Jinhua Zhao
Summary: An oligosaccharide HS-11, derived from sea cucumber Holothuria fuscopunctata, inhibits thrombin-mediated platelet activation and aggregation by directly binding to thrombin exosite II, demonstrating its antiplatelet and antithrombotic activity.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Stephanie A. Renna, Steven E. McKenzie, James V. Michael
Summary: Protease-activated receptors (PARs) are membrane proteins cleaved by proteases, such as thrombin, which activate them by revealing a tethered ligand. PARs play critical roles in platelet function and are potential targets for anti-platelet therapies. While genetically modified mouse models have provided insights into platelet PAR physiology, there are limitations. This review summarizes the differences in PAR expression and function between mice and humans, and highlights new tools for studying human physiology in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Rupsa C. Boelig, Tara J. Cahanap, Lin Ma, Tingting Zhan, Vincenzo Berghella, Joanna S. Y. Chan, Walter K. Kraft, Steven E. Mckenzie
Summary: The PAR4 Thr120 variant of the platelet receptor is associated with an increased risk of placental vascular pathology and preterm birth in homozygous individuals.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Hongbo Fang, Zibo Yuan, Yaohua Zhu, Hongwei Tang, Chun Pang, Jie Li, Jihua Shi, Wenzhi Guo, Shuijun Zhang
Summary: This study reveals the involvement of protease-activated receptor 4 (PAR4) in liver injury induced by brain death (BD). Blockade of PAR4 signaling mitigates liver damage, suppresses inflammation and apoptosis, and improves platelet activation and accumulation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Thomas Gremmel, Alan D. Michelson, Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Maximilian Tscharre, Silvia Lee, Simon Panzer, Andrew L. Frelinger
Summary: The study found that in the absence of ACS, women had higher platelet activation in response to TRAP, while there was no significant difference between men and women in ACS patients. The occurrence of ischemic endpoints did not differ significantly between men and women in ACS patients.
Article
Pharmacology & Pharmacy
Melissa S. O'Brien, Jason J. McDougall
Summary: The study compared the role of PAR4 in early and late stage osteoarthritis pain, and found that PAR4 may be a viable target for treating early onset OA pain or episodic inflammatory flares.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Jing Yang, Claudio Mapelli, Zhaoqing Wang, Chi Shing Sum, Ji Hua, R. Michael Lawrence, Yan Ni, Dietmar A. Seiffert
Summary: Protease-activated receptor 4 (PAR4) is a promising drug target for improving the efficacy and safety of antiplatelet agents. However, the current PAR4 agonist peptides have limited utility in pharmacodynamic assays due to their high concentrations required to elicit an agonist response. This study developed a more potent PAR4 agonist peptide and a platelet aggregation assay for evaluating PAR4 antagonists, providing a valuable tool for the clinical development of PAR4 antagonists.
Article
Hematology
Tanvi Rudran, Silvio Antoniak, Matthew J. Flick, Mark H. Ginsberg, Alisa S. Wolberg, Wolfgang Bergmeier, Robert H. Lee
Summary: This study investigated the specific receptors and signaling pathways required for platelet function in thromboelastography (TEG) using genetic and pharmacologic inhibition of platelet proteins in mouse and human blood samples. The results showed that standard TEG is not sensitive to platelet signaling pathways critical for integrin inside-out activation and platelet hemostatic function. Furthermore, this study provides the first evidence that PARs and glycoprotein VI play redundant roles in platelet-mediated clot contraction in TEG.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Pharmacology & Pharmacy
A. Barra, K. M. Freitas, D. G. Marconato, P. Faria-Pinto, M. T. P. Lopes, Andre Klein
Summary: The PAR4 plays a potential role in antiplatelet therapy and also mediates the inflammatory response triggered by LPS in macrophages, presenting a new approach in understanding innate immune mechanisms.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Hematology
Silvia Maria Grazia Trivigno, Mauro Vismara, Ilaria Canobbio, Serena Rustichelli, Federico Galvagni, Maurizio Orlandini, Mauro Torti, Gianni Francesco Guidetti
Summary: The study found that CD93 supports platelet activation triggered by PAR4 stimulation and is required to stabilize the expression of the thrombin receptor on the cell surface.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Pharmacology & Pharmacy
Ying-Ting Lin, Yu Li, Hui-Ching Hsu, Ju-Ying Tsai, Jia-Hau Lee, Chi-Jung Tai, Ming-Jung Wu, Chin-Chung Wu
Summary: There is increasing evidence of the importance of protease-activated receptor 4 (PAR4) as a therapeutic target in thrombotic cardiovascular diseases. In this study, a flavonoid called 7, 4'-dimethoxy-3-hydroxyflavone was discovered as a new PAR4 antagonist from natural origin. It showed antiplatelet activity by inhibiting PAR4-mediated platelet aggregation and downstream signaling pathways. In addition, it displayed effective antithrombotic properties with less bleeding tendency in vivo, making it a potential candidate for developing new antiplatelet agents.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Gastroenterology & Hepatology
Ying Xie, Lindsey Fontenot, Andrea Chupina Estrada, Becca Nelson, Jiani Wang, David Q. Shih, Wendy Ho, S. Anjani Mattai, Florian Rieder, Dane D. Jensen, Nigel W. Bunnett, Hon Wai Koon
Summary: The study demonstrates that Elafin can suppress collagen synthesis in intestinal fibroblasts by inhibiting protease-activated receptor 2, which is dependent on cathelin S, leading to a reduction in intestinal fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Hematology
Sonali R. Gnanenthiran, Gabrielle J. Pennings, Caroline J. Reddel, Heather Campbell, Maaike Kockx, Justin R. Hamilton, Vivien Chen, Leonard Kritharides
Summary: Aging is associated with increased basal platelet activation, ADP hyperreactivity, and thrombin resistance. In situ thrombin generation and systemic inflammation may be potential targets for preventing cardiovascular disease in the elderly.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cell Biology
Christopher C. Pan, Raquel Maeso-Diaz, Tylor R. Lewis, Kun Xiang, Lianmei Tan, Yaosi Liang, Liuyang Wang, Fengrui Yang, Tao Yin, Calvin Wang, Kuo Du, De Huang, Seh Hoon Oh, Ergang Wang, Bryan Jian Wei Lim, Mengyang Chong, Peter B. Alexander, Xuebiao Yao, Vadim Y. Arshavsky, Qi-Jing Li, Anna Mae Diehl, Xiao-Fan Wang
Summary: Cellular senescence is a stable cell cycle arrest phenotype induced by stress, which creates a pro-inflammatory microenvironment and contributes to chronic inflammation and age-associated diseases. The molecular pathway involving thrombomodulin (THBD) signaling plays a crucial role in determining the fate of senescent cells, and inhibiting this pathway can effectively eliminate senescent cells and restore tissue homeostasis. These findings provide a potential target for developing senolytic agents to treat senescence-associated diseases.
Article
Biochemistry & Molecular Biology
Yi-Chun Chiang, Yu-Shan Wu, Ya-Fei Kang, Hui-Chun Wang, Meng-Chun Tsai, Chin-Chung Wu
Summary: This study discovered that fully methylated resveratrol analog, TMS, can selectively inhibit PAR4-mediated platelet activation and blood coagulation at low concentrations, as well as reduce thrombus formation. These findings suggest that fully methylated resveratrol analogs with anti-PAR4 activity could be potential candidates for the development of novel antiplatelet agents.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)