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(Circulation. 1998;97:16-18.)
© 1998 American Heart Association, Inc.

Editorials

Learning From the Transgenic Mouse

Endothelium, Adhesive Molecules, and Neointimal Formation

Valentin Fuster, MD, PhD; Michael Poon, MD; ; James T. Willerson, MD

From the Cardiovascular Institute (V.F.), Mount Sinai Medical Center, New York, NY; Cardiovascular Institute, Mount Sinai Medical Center, New York (M.P.); and St. Luke's Episcopal Hospital/Texas Heart Institute (J.T.W.), Houston, Tex.

Correspondence to Valentin Fuster, MD, PhD, Director, Cardiovascular Institute, Mount Sinai Medical Center, 1 Gustave Levy Place, Box 1030, New York, NY 10029-6574. E-mail Valentin_Fuster@smtplink.mssm.edu

Key Words: endothelium • plaque • genes

Vascular remodeling plays an important role in the development of native atherosclerosis and restenosis after PTCA. A typical atherosclerotic plaque consists of a core of lipid-rich macrophages surrounded by a thickened intima under the cover of a fibrous cap. Endothelial cell injury, related to shear forces and modified by certain risk factors,¹ appears to be a critical initial event in atherogenesis. The surface of dysfunctional endothelium serves as a point of entry for circulating inflammatory cells, such as lymphocytes and monocytes. The recruitment of circulating monocytes and subsequent transmigration of monocytes through the dysfunctional endothelium require the careful orchestration of circulating and secreted factors and various cellular components found in the circulation and the vessel wall.

Cell adhesion molecules have emerged as essential factors in the development of atherosclerosis and restenosis. In particular, P-selectin has been established as an important marker of chronic and acute atherosclerotic events. P-selectin is present in the -granules of inactivated platelets and in the Weibel-Palade bodies of endothelial cells. It is quickly redistributed to the surface of platelets and endothelial cells in response to activation by agonists, such as thrombin.² Increased expression of P-selectin and ICAM-1 has been shown in endothelium overlying atherosclerotic plaques but not in normal arterial endothelium or in endothelium overlying inactive fibrous plaques from the carotid and coronary arteries of postmortem specimens and patients undergoing vascular surgery.³ Poston and Johnson-Tidey⁴ further demonstrated that anti–P-selectin antibody blocks the in vitro binding of monocytes to the endothelium but not to the denuded intima . . . [Full Text of this Article]

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