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Updated: Jul 31, 2026
10:37
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Ether lipid metabolism by AADACL1 regulates platelet function and thrombosis
Stephen P Holly1,2, Nidhi Gera1,3, Putianqi Wang1
1Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Blood Advances
|November 27, 2019
Summary
Inhibition of arylacetamide deacetylase-like 1 (AADACL1) regulates ether lipids, impairing platelet activation and thrombosis. This study reveals AADACL1
Area of Science:
- Biochemistry
- Hematology
- Pharmacology
Background:
- Arylacetamide deacetylase-like 1 (AADACL1) is a novel lipid deacetylase in platelets.
- Previous studies showed AADACL1 inhibition affects platelet aggregation and signaling.
- The precise in vivo mechanisms of AADACL1 in platelet function remain unclear.
Purpose of the Study:
- To elucidate the in vivo mechanisms by which AADACL1 regulates platelet signaling and function.
- To investigate the role of AADACL1 in ether lipid metabolism and its impact on platelet activation.
- To evaluate the therapeutic potential of AADACL1 inhibition in thrombosis models.
Main Methods:
- Treatment of human platelets with AADACL1 inhibitor JW480 or substrate 1-O-hexadecyl-2-acetyl-sn-glycerol (HAG).
- Assessment of platelet aggregation, granule secretion, Ca2+ flux, and PKC phosphorylation.
- Utilized P2Y12-/- and CalDAG GEFI-/- mice models; conducted FeCl3-induced arterial thrombosis and tail bleeding time assays in rats.
Main Results:
- AADACL1 inhibition/modulation led to decreased platelet aggregation, secretion, Ca2+ flux, and PKC phosphorylation.
- HAG-mediated inhibition was primarily through the P2Y12 pathway, with HAGP metabolite blocking PKC activity.
- AADACL1 inhibition in rats reduced platelet aggregation, protected against arterial thrombosis, and delayed bleeding.
Conclusions:
- AADACL1 inhibition alters the platelet ether lipidome, promoting HAGP accumulation.
- This accumulation impairs PKC activation and granule secretion, crucial for platelet recruitment.
- AADACL1 inhibition demonstrates therapeutic potential for treating thrombotic disorders.
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