Noncanonical Matrix Metalloprotease 1–Protease-Activated Receptor 1 Signaling Drives Progression of Atherosclerosis
| Autor: | Georgios Koukos, Andrew Shearer, Athan Kuliopulos, Susan E. Turner, Jeffrey J. Rade, Elizabeth K. Fletcher, Tianfang Huang, Rajashree Rana, Carey Kimmelstiel, Kevin P. Bliden, Lidija Covic, Paul A. Gurbel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Acute coronary syndrome business.industry medicine.medical_treatment Percutaneous coronary intervention 030204 cardiovascular system & hematology Matrix metalloproteinase medicine.disease Thrombosis Coronary artery disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Protease-Activated Receptor 1 Thrombin Hemostasis medicine Cancer research Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38:1368-1380 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.118.310967 |
| Popis: | Objective— Protease-activated receptor-1 (PAR1) is classically activated by thrombin and is critical in controlling the balance of hemostasis and thrombosis. More recently, it has been shown that noncanonical activation of PAR1 by matrix metalloprotease-1 (MMP1) contributes to arterial thrombosis. However, the role of PAR1 in long-term development of atherosclerosis is unknown, regardless of the protease agonist. Approach and Results— We found that plasma MMP1 was significantly correlated ( R =0.33; P =0.0015) with coronary atherosclerotic burden as determined by angiography in 91 patients with coronary artery disease and acute coronary syndrome undergoing cardiac catheterization or percutaneous coronary intervention. A cell-penetrating PAR1 pepducin, PZ-128, currently being tested as an antithrombotic agent in the acute setting in the TRIP-PCI study (Thrombin Receptor Inhibitory Pepducin-Percutaneous Coronary Intervention), caused a significant decrease in total atherosclerotic burden by 58% to 70% ( P P Conclusions— These data suggest that targeting the MMP1–PAR1 system may be effective in tamping down chronic inflammatory signaling in plaques and halting the progression of atherosclerosis. |
| Databáze: | OpenAIRE |
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