HYPERTENSION-ENHANCED MONOCYTE ADHESION IN EXPERIMENTAL ATHEROSCLEROSIS

Purpose: Hypertension is a known clinical risk factor for atherosclero sis. In experimental atherosclerosis, monocyte adhesion to the endothe lial surface is enhanced and is considered to be an important early st age in plaque formation. We tested the hypothesis that hypertension en hances monocyte adhesion in experimental atherosclerosis. Methods: Twe nty-two New Zealand White rabbits were fed an atherogenic diet for 3 w eeks to induce plaque formation. Aortic coarctation was created in eig ht rabbits by wrapping a Dacron band around the midportion of the desc ending thoracic aorta (stenosis group), whereas six rabbits underwent banding without aortic constriction (no stenosis group). Eight rabbits served as nonoperated controls. Monocyte binding to the aortic endoth elial surface was counted with epifluorescent microscopy on standard a ortic segments proximal and distal to the band. Immunohistochemistry w as performed for the following antibodies: VCAM-1, RAM11, CD11b, and f actor VIII. Results: Mean blood pressure was 89 +/- 3 mm Hg in the aor ta proximal to the stenosis, compared with 64 +/- 4 mm Hg in the no st enosis group and 74 +/- 3 mm Hg in the control group (P < 0.01). The m ean aortic blood pressure gradient across the stenosis was 16 +/- 2 mm Hg in the stenosis group, whereas the aortic blood pressure gradient was 0.2 +/- 0.6 mm Hg in the no stenosis group and -0.3 +/- 0.4 mm Hg in the control group (p < 0.001). Monocyte adhesion to the aortic endo thelial surface proximal to the stenosis was increased twofold compare d with adhesion to the aorta distal to the stenosis and compared with the proximal aorta in the control group (P < 0.02). The proximal-to-di stal aortic ratio of monocyte binding was enhanced in the stenosis gro up (2.2) compared with the no stenosis (0.76) and control (0.83) group s (p < 0.01). The intima area of the aorta proximal to the stenosis wa s significantly increased compared with the proximal aortas in the no stenosis and control groups (P < 0.01). RAM11, CD11b, and endothelial VCAM-1 expression were enhanced in the hypertensive region proximal to the stenosis. Conclusions: In the hypertensive region in the aorta pr oximal to the stenosis, monocyte adhesion and endothelial VCAM-1 expre ssion were increased, with intimal thickening and accumulation of macr ophages. These findings suggest that hypertension may promote atherosc lerotic plaque formation by enhancing monocyte adhesion.