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Updated: Feb 9, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Ticagrelor, a P2Y12 antagonist, attenuates vascular dysfunction and inhibits atherogenesis in
Byambasuren Ganbaatar1, Daiju Fukuda2, Hotimah Masdan Salim1
1Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan.
Insights
Ticagrelor reduces cardiovascular events by inhibiting endothelial cell inflammation and vascular dysfunction. This study shows ticagrelor attenuates atherosclerosis in mice, suggesting a potential mechanism for its clinical benefits.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Atherosclerosis Research
Background:
- P2Y12 receptor expression on vascular cells, beyond platelets, suggests a role in atherogenesis.
- Ticagrelor, known to reduce cardiovascular events in acute coronary syndrome (ACS), may have broader vascular protective effects.
Purpose of the Study:
- To investigate if ticagrelor can attenuate vascular dysfunction.
- To determine if ticagrelor inhibits atherogenesis in apolipoprotein E-deficient (apoE-/-) mice.
Main Methods:
- ApoE-/- mice were fed a western-type diet with or without ticagrelor.
- Atherosclerotic lesions, endothelial function, inflammatory markers, and JNK phosphorylation were analyzed.
- In vitro studies used human umbilical vein endothelial cells (HUVEC) to assess ticagrelor's effects on adenosine diphosphate (ADP)-induced responses.
Main Results:
- Ticagrelor treatment significantly attenuated atherosclerotic lesion progression and endothelial dysfunction.
- Reduced expression of inflammatory molecules (e.g., VCAM-1) and JNK phosphorylation was observed in ticagrelor-treated mice.
- Ticagrelor inhibited ADP-induced inflammatory responses and JNK activation in HUVEC.
Conclusions:
- Ticagrelor attenuates vascular dysfunction and atherogenesis by inhibiting endothelial cell inflammatory activation.
- These findings suggest a potential mechanism for ticagrelor's efficacy in reducing cardiovascular events in ACS patients.
Background And Aims:
Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/-) mice.
Methods:
Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0.1% ticagrelor (approximately 120 mg/kg/day). Non-treated animals on WTD served as control. Atherosclerotic lesions were examined by en-face Sudan IV staining, histological analyses, quantitative RT-PCR analysis, and western blotting. Endothelial function was analyzed by acetylcholine-dependent vasodilation using aortic rings. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments.
Results:
Ticagrelor treatment for 20 weeks attenuated atherosclerotic lesion progression in the aortic arch compared with control (p < 0.05). Ticagrelor administration for 8 weeks attenuated endothelial dysfunction (p < 0.01). Ticagrelor reduced the expression of inflammatory molecules such as vascular cell adhesion molecule-1, macrophage accumulation, and lipid deposition. Ticagrelor decreased the phosphorylation of JNK in the aorta compared with control (p < 0.05). Ticagrelor and a JNK inhibitor ameliorated impairment of endothelium-dependent vasodilation by adenosine diphosphate (ADP) in wild-type mouse aortic segments. Furthermore, ticagrelor inhibited the expression of inflammatory molecules which were promoted by ADP in HUVEC (p < 0.001). Ticagrelor also inhibited ADP-induced JNK activation in HUVEC (p < 0.05).
Conclusions:
Ticagrelor attenuated vascular dysfunction and atherogenesis through the inhibition of inflammatory activation of endothelial cells. These effects might be a potential mechanism by which ticagrelor decreases cardiovascular events in patients with ACS.
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