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Vascular Medicine
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Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators

Carmine Cardillo

National Heart, Lung, and Blood Institute, Bethesda, MD, USA, Catholic University, Rome, Italy

Marco Mettimano

Catholic University, Rome, Italy

Nadia Mores

Catholic University, Rome, Italy

Kwang K Koh

National Heart, Lung, and Blood Institute, Bethesda, MD, USA, Gachon Medical Center, Inchon, South Korea

Umberto Campia

National Heart, Lung, and Blood Institute, Bethesda, MD, USA, Cardiovascular Research Institute, Washington, DC, USA

Julio A Panza

National Heart, Lung, and Blood Institute, Bethesda, MD, USA, Cardiovascular Research Institute, Washington, DC, USA, julio.a.panza{at}medstar.net

Endothelial expression of cell adhesion molecules (CAMs) plays an important role in atherosclerosis. Atherosclerosis is increased in hyperinsulinemic states, but whether insulin per se is proatherogenic remains unclear. To investigate the effects of hyperinsulinemia on CAM expression, plasma levels of ICAM-1, VCAM-1 and E-selectin were measured before and after forearm infusion of insulin in healthy subjects. Insulin administration for 2 h resulted in signifi-cant hyperinsulinemia, whereas no significant change was observed in soluble CAMs (all p > 0.05). Because insulin stimulates endothelial release of both endothelin-1 (ET-1) and nitric oxide (NO), which may modulate the expression of CAMs, we also investigated the response of CAMs to ET-1 receptor blockade, alone and in combination with NO synthesis inhibition. ET-1 receptor blockade during hyperinsulinemia resulted in a vasodilator response, but did not affect soluble CAMs (all p > 0.05). Superimposition of NO inhibition by l-NMMA reversed the vasodilator effect of ET-1 blockade, without affecting soluble CAMs (all p > 0.05). In conclusion, acute hyperinsulinemia, alone or during ET-1 and NO pathway blockade, does not affect soluble CAMs. These results do not support a direct effect of insulin on endothelial cells to affect leukocyte adhesiveness to the vascular wall.

Key Words: cell adhesion molecules • endothelin • endothelium • insulin • nitric oxide

Vascular Medicine, Vol. 9, No. 3, 185-188 (2004)
DOI: 10.1191/1358863x04vm546oa


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