Modulation of expression of endothelial intercellular adhesion molecule-1,platelet-endothelial cell adhesion molecule-1, and vascular cell adhesion molecule-1 in aortic arch lesions of apolipoprotein E-deficient compared with wild-type mice

Human vascular adhesion molecules, such as intercellular adhesion molecule- 1 (ICAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and va scular cell adhesion molecule-1 (VCAM-1), are thought to play a critical ro le in the homing of leukocytes to sites of atherosclerotic lesions. However , very little is known about the expression of adhesion molecules in the va sculature of mice models, such as apolipoprotein E knockout (apoE(-/-)) mic e, the lesions of which closely mimic human atherosclerotic lesions. This s tudy has first quantitatively characterized the mean expression of endothel ial 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 ap oE-deficient compared with wild-type (C57BL/6) mice. These animals were fed a chow or a cholesterol-rich diet. ApoE(-/-) animals showed first an incre ase (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 modulat ion of the mean expression of adhesion molecules was not observed in wild-t ype mice. Confirmation of immunohistochemistry results on ICAM-1 was obtain ed by Northern blots performed on the aortic arch of apoE and C57BL6 chow-f ed mice over a period of 20 weeks. Moreover, the presence of VCAM-1 was als o confirmed at the RNA level, on aortas of control and apoE mice, by revers e transcription-polymerase chain reaction. In the second part of the study, we assayed the levels of adhesion molecules, in different types of histolo gically defined atherosclerotic lesions, in apoE(-/-) animals fed for 20 we eks. All 3 adhesion molecules (ICAM-1, PECAM-1, and VCAM-1) were observed t o be reduced in fibrofatty and complex lesions but not in fatty streaks or in areas without lesions. These results indicate that the expression of the se adhesion molecules in apoE-deficient animals varies with the evolution o f the plaque from a fatty to a fibrous stage.