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Publication
Ticagrelor induces paraoxonase-1 (PON1) and better protects hypercholesterolemic
mice against atherosclerosis compared to clopidogrel.
Authors Halim H, Pinkaew D, Chunhacha P, Sinthujaroen P, Thiagarajan P, Fujise K
Submitted By Submitted Externally on 2/12/2020
Status Published
Journal PLoS ONE
Year 2019
Date Published
Volume : Pages 14 : e0218934
PubMed Reference 31242230
Abstract Ticagrelor (TIC), a P2Y purinoceptor 12 (P2Y12)-receptor antagonist, has been
widely used to treat patients with acute coronary syndrome. Although animal
studies suggest that TIC protects against atherosclerosis, it remains unknown
whether it does so through its potent platelet inhibition or through other
pathways. Here, we placed hypercholesterolemic Ldlr-/-Apobec1-/- mice on a
high-fat diet and treated them with either 25 mg/kg/day of clopidogrel (CLO) or
180 mg/kg/day of TIC for 16 weeks and evaluated the extent of atherosclerosis.
Both treatments equally inhibited platelets as determined by ex vivo platelet
aggregation assays. The extent of atherosclerosis, however, was significantly
less in the TIC group than in the CLO group. Immunohistochemical staining and
ELISA showed that TIC treatment was associated with less macrophage infiltration
to the atherosclerotic intima and lower serum levels of CCL4, CXCL10, and TNFa,
respectively, than CLO treatment. Treatment with TIC, but not CLO, was
associated with higher serum activity and tissue level of paraoxonase-1 (PON1),
an anti-atherosclerotic molecule, suggesting that TIC might exert greater
anti-atherosclerotic activity, compared with CLO, through its unique ability to
induce PON1. Although further studies are needed, TIC may prove to be a viable
strategy in the prevention and treatment of chronic stable human
atherosclerosis.




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