| First Author | Watanabe S | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 531 |
| Issue | 2 | Pages | 125-132 |
| PubMed ID | 32782151 | Mgi Jnum | J:304240 |
| Mgi Id | MGI:6694448 | Doi | 10.1016/j.bbrc.2020.07.063 |
| Citation | Watanabe S, et al. (2020) ASC regulates platelet activation and contributes to thrombus formation independent of NLRP3 inflammasome. Biochem Biophys Res Commun 531(2):125-132 |
| abstractText | BACKGROUND: Platelets are critical mediators of vascular homeostasis and thrombosis, and also contribute to the development of inflammation. NLRP3 inflammasome is a cytosolic multi-protein complex that consists of NLRP3, ASC and caspase-1, and regulates IL-1beta-mediated inflammation. METHOD AND RESULTS: Using two mouse models of thrombosis (i.e., occlusion of the middle cerebral artery and inferior vena cava), we found that thrombus formation was significantly enhanced in ASC-deficient (ASC(-/-)) mice, compared to that in wild-type (WT) and IL-1beta(-/-) mice. ASC deficiency had no effects on blood coagulation parameters (i.e., prothrombin time [PT] and activated partial thromboplastin time [APTT]). Platelets from WT mice express ASC, but neither NLRP3 nor caspase-1. ASC deficiency significantly enhanced the expression of P-selectin and GPIIb/IIIa in response to a GPVI agonist (collagen-related peptide [CRP]), but not to thrombin, in platelets. CRP induced ASC speck formation in WT platelets. ASC deficiency also enhanced cytosolic Ca(2+) elevation and phosphorylation of ERK1/2 and Akt in platelets. CONCLUSION: Our results demonstrate that ASC negatively regulates GPVI signaling in platelets and enhances thrombus formation, independent of NLRP3 inflammasome and IL-1beta, and provide novel insights into the link between inflammation and thrombosis. |
