Arterial injury increases expression of inflammatory adhesion molecules inthe carotid arteries of apolipoprotein-E-deficient mice

Recent studies demonstrate increased cellular adhesion molecule expression by neointimal endothelium overlying primary and restenotic atherosclerotic plaque. In this study, we developed an atherosclerotic mouse model of arter ial injury and characterized adhesion molecule expression after injury. Six teen apolipoprotein-E-(ApoE)-deficient mice fed a Western-type diet for 4 w eeks underwent carotid artery wire denudation at week 2. For each segment, the extent of neointima formation and medial thickening, or adhesion molecu le expression, were scored separately on a scale from 0 (no plaque/thickeni ng or expression) to 3 (extensive plaque/thickening or expression) using Mo vat staining (n = 3) or immunohistochemical analysis (n = 13). Histology re vealed significant medial thickening (1.8 +/- 0.9 vs. 0.3 +/- 0.5, p < 0.00 1) versus controls a nd pronounced staining for monocytes/macrophages in th e wall of injured vessels. Immunohistochemical analysis showed more robust expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the luminal surface of injured arteries ver sus controls (2.2 +/- 0.6 vs. 1.4 +/- 0.7, p < 0.01, and 2.5 +/- 0.5 vs. 1. 2 +/- 0.6, p < 0.001, respectively). Injury increased adventitial ICAM-1 ex pression (2.6 +/- 0.5 vs. 1.6 +/- 0.5, p < 0.002) and medial VCAM-1 express ion (2.2 +/- 0.6 vs. 1.2 +/- 0.7, p < 0.004). Thus, carotid injury results in significant medial thickening and increases adhesion molecule expression beyond that induced in ApoE-deficient mice fed a Western diet alone. The o bservation of macrophage infiltration into the media at sites of increased ICAM-1 and VCAM-1 expression suggests that these molecules may mediate mono cyte/macrophage trafficking into the wall of injured arteries. Copyright(C) 1999 S. Karger AG. Basel.