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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable
Florian Bea1, Erwin Blessing, Brian J Bennett
1Department of Pathobiology and the Interdisciplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195, USA.
Objective:
Inflammation contributes to atherosclerotic plaque initiation and progression. Recent studies suggest that anti-inflammatory drugs such as cyclooxygenase-2 (Cox-2) inhibitors have anti-atherogenic effects. The current study was designed to investigate whether administration of a Cox-2 inhibitor to older apolipoprotein E deficient (apo E-/-) mice with established lesions alters the composition and increases the stability of the lesions.
Methods And Results:
The Cox-2 inhibitor Celecoxib was administered in chow to 26-week-old, male, apo E-/- mice exhibiting advanced, unstable atherosclerotic lesions within the innominate/brachiocephalic artery. Mice administered Celecoxib had no significant changes in serum cholesterol or the average cross sectional area of atherosclerotic lesion in the innominate artery after 15 weeks of treatment in comparison to non-treated control mice. Histological analyses of sections of the innominate artery demonstrated no significant changes in the frequency of markers of advanced and unstable atherosclerotic plaques, including intra-plaque hemorrhage, vascular calcification, thinning of the fibrous cap, size of the necrotic core and macrophage content. There were also no significant differences in the content of Cox-2 within the lesions. Quantitative real time polymerase chain reaction with mRNA isolated from the aorta of each mouse revealed no significant changes in the expression of tissue factor and inducible nitric oxide synthase. However, mRNA levels for MCP-1 were increased fivefold following 15 weeks of treatment with Celecoxib in comparison to non-treated control mice.
Conclusions:
These data suggest that Celecoxib has no effect on the composition of advanced atherosclerotic lesions in older apo E-/- mice.
Insights
Celecoxib, a cyclooxygenase-2 (Cox-2) inhibitor, did not alter advanced atherosclerotic lesion composition or stability in older apolipoprotein E deficient (apo E-/-) mice. Further research is needed to explore potential therapeutic effects of Cox-2 inhibitors in atherosclerosis.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Pharmacology
Background:
- Inflammation plays a critical role in the development and progression of atherosclerotic plaques.
- Cyclooxygenase-2 (Cox-2) inhibitors are anti-inflammatory drugs with potential anti-atherogenic properties.
- Investigating their effects on established lesions is crucial for understanding therapeutic potential.
Purpose of the Study:
- To determine if a Cox-2 inhibitor impacts the composition and stability of advanced atherosclerotic lesions.
- To evaluate the effects of Celecoxib in older apolipoprotein E deficient (apo E-/-) mice with pre-existing lesions.
Main Methods:
- Administration of Celecoxib in chow to 26-week-old male apo E-/- mice for 15 weeks.
- Analysis of serum cholesterol, lesion size, and histological markers of plaque instability.
- Quantitative real-time polymerase chain reaction (PCR) to assess gene expression (tissue factor, inducible nitric oxide synthase, MCP-1).
Main Results:
- No significant changes in serum cholesterol or lesion cross-sectional area were observed.
- Histological analysis revealed no alterations in plaque instability markers (hemorrhage, calcification, cap thinning, necrotic core, macrophage content).
- While MCP-1 mRNA levels increased fivefold, expression of tissue factor and inducible nitric oxide synthase remained unchanged. Cox-2 expression within lesions was also unaffected.
Conclusions:
- Celecoxib treatment did not affect the composition or stability of advanced atherosclerotic lesions in this mouse model.
- The observed increase in MCP-1 warrants further investigation into potential subtle effects or alternative mechanisms.
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