Unraveling the Interaction of Aspirin, Ticagrelor, and Rosuvastatin on the Progression of Atherosclerosis and Inflammation in Diabetic Mice

Yumei Ye, Sven Nylander, Yochai Birnbaum

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: We explored the effects of rosuvastatin, aspirin, ticagrelor, and clopidogrel, alone or in combinations on the progression of atherosclerosis and inflammasome activation in diabetic mice. Statins and ticagrelor increase the production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15-epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely blocked. Methods: ApoE−/−/db+/db+ double-knockout mice received rosuvastatin (5 mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75 mg/kg/day), or their combination for 14 weeks. Serum 15-epi-lipoxin A4 levels and aortic wall cholesterol content, IL-1β, IL-6, and TNF-α levels, and plaque area were assessed. Results: Aspirin, ticagrelor, and rosuvastatin increased 15-epi-lipoxin A4 levels. The combination of rosuvastatin + ticagrelor provided an additive effect. Aspirin attenuated the effect of both ticagrelor and rosuvastatin. Aspirin, ticagrelor, and rosuvastatin reduced the area of the atherosclerotic plaque. The combination of ticagrelor + rosuvastatin provided additive effects. There was a negative interaction when aspirin was combined with ticagrelor or rosuvastatin. Aspirin, ticagrelor, and rosuvastatin decreased serum IL-1β and IL-6 levels. There was no interaction between aspirin and ticagrelor or aspirin and rosuvastatin, whereas combining rosuvastatin and ticagrelor provided an additive effect. Aspirin, ticagrelor, and rosuvastatin all decreased TNF-α levels. Aspirin attenuated the effect of both ticagrelor and rosuvastatin, and there was no additive effect of combining ticagrelor + rosuvastatin. Conclusions: We found an intricate interaction between aspirin, ticagrelor, and rosuvastatin, as aspirin reduced both ticagrelor and rosuvastatin ability to ameliorate inflammation and atherosclerosis. In contrast, we found additive effects when ticagrelor and rosuvastatin were combined.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalCardiovascular Drugs and Therapy
DOIs
StateAccepted/In press - Nov 28 2017

Fingerprint

Aspirin
Atherosclerosis
Inflammation
clopidogrel
Ticagrelor
Rosuvastatin Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cyclooxygenase 2
Interleukin-1
Interleukin-6
Inflammasomes
Apolipoproteins E
Atherosclerotic Plaques
Serum
Knockout Mice

Keywords

  • Adenosine
  • Aspirin
  • Atherosclerosis
  • Clopidogrel
  • Inflammation
  • Statin
  • Ticagrelor

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

@article{7e8f606bebf54cc49cb786e47b5f6b1a,
title = "Unraveling the Interaction of Aspirin, Ticagrelor, and Rosuvastatin on the Progression of Atherosclerosis and Inflammation in Diabetic Mice",
abstract = "Purpose: We explored the effects of rosuvastatin, aspirin, ticagrelor, and clopidogrel, alone or in combinations on the progression of atherosclerosis and inflammasome activation in diabetic mice. Statins and ticagrelor increase the production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15-epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely blocked. Methods: ApoE−/−/db+/db+ double-knockout mice received rosuvastatin (5 mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75 mg/kg/day), or their combination for 14 weeks. Serum 15-epi-lipoxin A4 levels and aortic wall cholesterol content, IL-1β, IL-6, and TNF-α levels, and plaque area were assessed. Results: Aspirin, ticagrelor, and rosuvastatin increased 15-epi-lipoxin A4 levels. The combination of rosuvastatin + ticagrelor provided an additive effect. Aspirin attenuated the effect of both ticagrelor and rosuvastatin. Aspirin, ticagrelor, and rosuvastatin reduced the area of the atherosclerotic plaque. The combination of ticagrelor + rosuvastatin provided additive effects. There was a negative interaction when aspirin was combined with ticagrelor or rosuvastatin. Aspirin, ticagrelor, and rosuvastatin decreased serum IL-1β and IL-6 levels. There was no interaction between aspirin and ticagrelor or aspirin and rosuvastatin, whereas combining rosuvastatin and ticagrelor provided an additive effect. Aspirin, ticagrelor, and rosuvastatin all decreased TNF-α levels. Aspirin attenuated the effect of both ticagrelor and rosuvastatin, and there was no additive effect of combining ticagrelor + rosuvastatin. Conclusions: We found an intricate interaction between aspirin, ticagrelor, and rosuvastatin, as aspirin reduced both ticagrelor and rosuvastatin ability to ameliorate inflammation and atherosclerosis. In contrast, we found additive effects when ticagrelor and rosuvastatin were combined.",
keywords = "Adenosine, Aspirin, Atherosclerosis, Clopidogrel, Inflammation, Statin, Ticagrelor",
author = "Yumei Ye and Sven Nylander and Yochai Birnbaum",
year = "2017",
month = "11",
day = "28",
doi = "10.1007/s10557-017-6763-9",
language = "English (US)",
pages = "1--12",
journal = "Cardiovascular Drugs and Therapy",
issn = "0920-3206",
publisher = "Kluwer Academic Publishers",

}

TY - JOUR

T1 - Unraveling the Interaction of Aspirin, Ticagrelor, and Rosuvastatin on the Progression of Atherosclerosis and Inflammation in Diabetic Mice

AU - Ye, Yumei

AU - Nylander, Sven

AU - Birnbaum, Yochai

PY - 2017/11/28

Y1 - 2017/11/28

N2 - Purpose: We explored the effects of rosuvastatin, aspirin, ticagrelor, and clopidogrel, alone or in combinations on the progression of atherosclerosis and inflammasome activation in diabetic mice. Statins and ticagrelor increase the production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15-epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely blocked. Methods: ApoE−/−/db+/db+ double-knockout mice received rosuvastatin (5 mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75 mg/kg/day), or their combination for 14 weeks. Serum 15-epi-lipoxin A4 levels and aortic wall cholesterol content, IL-1β, IL-6, and TNF-α levels, and plaque area were assessed. Results: Aspirin, ticagrelor, and rosuvastatin increased 15-epi-lipoxin A4 levels. The combination of rosuvastatin + ticagrelor provided an additive effect. Aspirin attenuated the effect of both ticagrelor and rosuvastatin. Aspirin, ticagrelor, and rosuvastatin reduced the area of the atherosclerotic plaque. The combination of ticagrelor + rosuvastatin provided additive effects. There was a negative interaction when aspirin was combined with ticagrelor or rosuvastatin. Aspirin, ticagrelor, and rosuvastatin decreased serum IL-1β and IL-6 levels. There was no interaction between aspirin and ticagrelor or aspirin and rosuvastatin, whereas combining rosuvastatin and ticagrelor provided an additive effect. Aspirin, ticagrelor, and rosuvastatin all decreased TNF-α levels. Aspirin attenuated the effect of both ticagrelor and rosuvastatin, and there was no additive effect of combining ticagrelor + rosuvastatin. Conclusions: We found an intricate interaction between aspirin, ticagrelor, and rosuvastatin, as aspirin reduced both ticagrelor and rosuvastatin ability to ameliorate inflammation and atherosclerosis. In contrast, we found additive effects when ticagrelor and rosuvastatin were combined.

AB - Purpose: We explored the effects of rosuvastatin, aspirin, ticagrelor, and clopidogrel, alone or in combinations on the progression of atherosclerosis and inflammasome activation in diabetic mice. Statins and ticagrelor increase the production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15-epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely blocked. Methods: ApoE−/−/db+/db+ double-knockout mice received rosuvastatin (5 mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75 mg/kg/day), or their combination for 14 weeks. Serum 15-epi-lipoxin A4 levels and aortic wall cholesterol content, IL-1β, IL-6, and TNF-α levels, and plaque area were assessed. Results: Aspirin, ticagrelor, and rosuvastatin increased 15-epi-lipoxin A4 levels. The combination of rosuvastatin + ticagrelor provided an additive effect. Aspirin attenuated the effect of both ticagrelor and rosuvastatin. Aspirin, ticagrelor, and rosuvastatin reduced the area of the atherosclerotic plaque. The combination of ticagrelor + rosuvastatin provided additive effects. There was a negative interaction when aspirin was combined with ticagrelor or rosuvastatin. Aspirin, ticagrelor, and rosuvastatin decreased serum IL-1β and IL-6 levels. There was no interaction between aspirin and ticagrelor or aspirin and rosuvastatin, whereas combining rosuvastatin and ticagrelor provided an additive effect. Aspirin, ticagrelor, and rosuvastatin all decreased TNF-α levels. Aspirin attenuated the effect of both ticagrelor and rosuvastatin, and there was no additive effect of combining ticagrelor + rosuvastatin. Conclusions: We found an intricate interaction between aspirin, ticagrelor, and rosuvastatin, as aspirin reduced both ticagrelor and rosuvastatin ability to ameliorate inflammation and atherosclerosis. In contrast, we found additive effects when ticagrelor and rosuvastatin were combined.

KW - Adenosine

KW - Aspirin

KW - Atherosclerosis

KW - Clopidogrel

KW - Inflammation

KW - Statin

KW - Ticagrelor

UR - http://www.scopus.com/inward/record.url?scp=85035131874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035131874&partnerID=8YFLogxK

U2 - 10.1007/s10557-017-6763-9

DO - 10.1007/s10557-017-6763-9

M3 - Article

SP - 1

EP - 12

JO - Cardiovascular Drugs and Therapy

JF - Cardiovascular Drugs and Therapy

SN - 0920-3206

ER -