CIGARETTE-SMOKING IS ASSOCIATED WITH INCREASED HUMAN MONOCYTE ADHESION TO ENDOTHELIAL-CELLS - REVERSIBILITY WITH ORAL L-ARGININE BUT NOT VITAMIN-C

Objectives. This study sought to assess the effect of cigarette smokin g on adhesion of human monocytes to human endothelial cells and to mea sure the effect of L-arginine and vitamin C supplementation on this in teraction. Background. Cigarette smoking has been associated with abno rmal endothelial function and increased leukocyte adhesion to endothel ium, both key early events in atherogenesis. Supplementation with both oral L-arginine (the physiologic substrate for nitric oxide) and vita min C (an aqueous phase antioxidant) may improve endothelial function; however, their benefit in cigarette smokers is not known. Methods. Se rum was collected from eight smokers (mean [+/-SD] age 33 +/- 5 years) with no other coronary risk factors and eight age- and gender-matched lifelong nonsmokers. The serum was added to confluent monolayers of h uman umbilical vein endothelial cells and incubated for 24 h. Human mo nocytes obtained by counterflow centrifugation elutriation were then a dded to these monolayers for 1 h, and adhesion then was measured by li ght microscopy. To assess reversibility, monocyte/endothelial cell adh esion was then measured for each subject 2 h after 2 g of oral vitamin C and 2 h after 7 g of oral L-arginine. Results. In smokers compared with control subjects; monocyte/ endothelial cell adhesion was increas ed (46.4 +/- 4.5% vs. 27.0 +/- 5.2%, p < 0.001), endothelial expressio n of intercellular adhesion molecule (ICAM)-1 was increased (0.31 +/- 0.02 vs. 0.22 +/- 0.03, p = 0.004), and vitamin C levels were reduced (33.7 +/- 24.1 vs. 53.4 +/- 11.5 mu mol/liter, p = 0.028). After oral L-arginine, monocyte/ endothelial cell adhesion was reduced in smokers (from 46.4 +/- 4.5% to 35.1 +/- 4.0%, p = 0.002), as was endothelial cell expression of ICAM-1 (from 0.31 +/- 0.02 to 0.27 +/- 0.01, p = 0. 001). After vitamin C, there was no significant change in monocyte/end othelial cell adhesion or ICAM-1 expression from baseline in the smoke rs despite an increase in vitamin C levels (to 115 +/- 7 mu mol/liter) . Conclusions. Cigarette smoking is associated with increased monocyte -endothelial cell adhesion when endothelial cells are exposed to serum from healthy young adults. This abnormality is acutely reversible by oral L-arginine but not by vitamin C. (C) 1997 by the American College of Cardiology.