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Updated: Oct 11, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Modulation of expression of endothelial intercellular adhesion molecule-1, platelet-endothelial cell adhesion
K Zibara1, E Chignier, C Covacho
1INSERM U331/Faculté de Médecine RTH Laënnec, Lyon, France. zibara@laennec.univ-lyon
Insights
Atherosclerosis research in apoE(-/-) mice reveals dynamic changes in vascular adhesion molecules like ICAM-1 and PECAM-1 over time. Expression decreases in advanced lesions, offering insights into disease progression.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Vascular adhesion molecules are crucial for leukocyte homing to atherosclerotic lesions in humans.
- Apolipoprotein E knockout (apoE(-/-)) mice models mimic human atherosclerotic lesions.
- Limited data exists on adhesion molecule expression dynamics in apoE(-/-) mouse vasculature.
Purpose of the Study:
- To quantitatively characterize endothelial adhesion molecule expression over time in apoE(-/-) mice.
- To compare adhesion molecule expression in apoE(-/-) mice with wild-type (C57BL/6) controls.
- To investigate adhesion molecule levels in different types of atherosclerotic lesions.
Main Methods:
- Quantitative analysis of endothelial adhesion molecules (ICAM-1, PECAM-1, VCAM-1) in mouse aortas.
- Dietary intervention: chow vs. cholesterol-rich diet for up to 20 weeks.
- Techniques included immunohistochemistry, Northern blots, and RT-PCR.
Main Results:
- ApoE(-/-) mice showed transient increases then reductions in ICAM-1 and PECAM-1 expression.
- VCAM-1 expression levels did not significantly change over time in apoE(-/-) mice.
- Adhesion molecules were reduced in advanced fibrofatty and complex lesions but not fatty streaks.
Conclusions:
- Adhesion molecule expression in apoE(-/-) mice is modulated during lesion development.
- Expression patterns vary with atherosclerotic plaque evolution from fatty to fibrous stages.
- These findings enhance understanding of atherosclerosis pathogenesis in mouse models.
Abstract:
Human vascular adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are thought to play a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known about the expression of adhesion molecules in the vasculature of mice models, such as apolipoprotein E knockout (apoE(-/-)) mice, the lesions of which closely mimic human atherosclerotic lesions. This study has first quantitatively characterized the mean expression of endothelial adhesion molecules, lining the whole vessel intimal circumference, over a period of time (0 to 20 weeks of diet) in aortic arch lesions of male apoE-deficient compared with wild-type (C57BL/6) mice. These animals were fed a chow or a cholesterol-rich diet. ApoE(-/-) animals showed first an increase (at 6 weeks) and then a reduction (at 16 weeks) in the mean expression of ICAM-1 (P<0.05) and PECAM-1 (P<0.05) but not VCAM-1 levels. Such modulation of the mean expression of adhesion molecules was not observed in wild-type mice. Confirmation of immunohistochemistry results on ICAM-1 was obtained by Northern blots performed on the aortic arch of apoE and C57BL6 chow-fed mice over a period of 20 weeks. Moreover, the presence of VCAM-1 was also confirmed at the RNA level, on aortas of control and apoE mice, by reverse transcription-polymerase chain reaction. In the second part of the study, we assayed the levels of adhesion molecules, in different types of histologically defined atherosclerotic lesions, in apoE(-/-) animals fed for 20 weeks. All 3 adhesion molecules (ICAM-1, PECAM-1, and VCAM-1) were observed to be reduced in fibrofatty and complex lesions but not in fatty streaks or in areas without lesions. These results indicate that the expression of these adhesion molecules in apoE-deficient animals varies with the evolution of the plaque from a fatty to a fibrous stage.
