Adhesion Molecules and Smoking - Adhesion Molecules - page 254

exposure— ICAM-1, VCAM-1, P-selectin, and E-selectin—are associated with
these diseases in epidemiological studies. Although the exact mechanisms have yet
to be fully characterized, the pathophysiology in part relies on these molecules.
Initially, epidemiological studies linked cigarette smoking to abnormal adhesion
molecule expression. h e molecular pathways leading to disease have since been
examined. Smoking leads to abnormal monocyte expression of pro-inl ammatory
cytokines, which in turn leads to abnormal adhesion molecule expression. h is
incites inl ammatory injury and disease. Each cellular adhesion molecule plays
its own role. In this chapter, we examine the inl uence of smoking on ICAM-1
and P-selectin expression and the initiation of atherosclerosis and chronic airway
inl ammation.
INTRODUCTION
Tissue damage caused by cigarette smoking, at a molecular level, results
from leukocyte-mediated damage of the endothelium and subendothelium.
Circulating leukocytes are recruited from the circulation and adhere to the
vascular endothelium. Following cellular adhesion, the leukocytes migrate to the
subendothelium and cause inl ammatory injury to the underlying tissues.
Adhesion molecules mediate the interactions between inl ammatory cells,
specii cally circulating leukocytes, and the endothelium. Changes in the expression
of these molecules alter the balance between homeostasis and disease. Adhesion
molecules are present in two forms: those bound to the epithelial cells and those
found in a soluble form, circulating within the blood or other body l uids. Soluble
adhesion molecules have been studied as biomarkers for disease activity and for
possible usefulness as prognostic indicators.
CARDIOVASCULAR DISEASE
Atherosclerosis
Background
Atherosclerosis is the result of inl ammatory damage to the vascular endothelium
and an important etiology of CVD. Elevated serum concentrations of soluble
adhesion molecules are associated with atherosclerosis and are predictive of future
cardiovascular events. Dif erent adhesion molecules play distinct roles in the
pathology of CVD (Fig. 1) ( Güray et al. 2004). While smoking increases circulating
concentrations of soluble adhesion molecules, cessation of smoking leads to a
decrease in concentrations of soluble adhesion molecules (Blann et al. 1997). h is
corresponds to the clinical phenomenon of decreased risk of atherosclerosis and
other ill ef ects of smoking that is observed following cessation. h is phenomenon