Levels of expression of P-selectin, E-selectin, and intercellular adhesion molecule-1 in coronary atherectomy specimens from patients with stable and unstable angina pectoris.

Unstable angina occurs when atherosclerotic plaque ruptures. Recent evidence suggests a role for inflammation in this process. Leukocyte-endothelial cell interactions are important in inflammation and are regulated by cell adhesion molecules. This study was designed to examine the vascular expression of cell adhesion molecules and cytokines in patients with unstable angina. Directional coronary atherectomy was performed in patients with unstable and stable angina. Expression of the cell adhesion molecules P-selectin, E-selectin, and intercellular adhesion molecule-1 in the tissue obtained was examined using immunohistochemistry. In addition, expression of the cytokines tumor necrosis factor-alpha and interleukin-1beta, which participate in the regulation of cell adhesion molecule expression, was also examined. Atherectomy specimens had significantly greater P-selectin expression from patients with unstable angina than from patients with stable angina. P-selectin expression was observed primarily on endothelial cells. There were no differences in any of the other factors between patients with unstable and stable angina. In addition, other clinical and angiographic variables were not associated with differential expression of any of the cell adhesion molecules or cytokines. These results indicate a possible role for P-selectin in the process of unstable angina.

A sialyl Lewis(x)-containing carbohydrate reduces infarct size: role of selectins in myocardial reperfusion injury.

Previous studies have implicated the selectins (P- and L-selectin) in the acute phase of myocardial reperfusion injury. However, it is unclear whether these adhesion molecules are involved in the pathogenesis of myocardial reperfusion associated with longer periods of reperfusion. Dogs (n = 8/group) were subjected to 90 min of coronary ischemia and 48 h of reperfusion. Animals were initially treated with a 35 mg/kg intravenous bolus of a sialyl Lewis(x) oligosaccharide (SLe(x)-OS) 10 min before reperfusion, followed by a 1.75 mg.kg-1.h-1 infusion for the first 24 h of reperfusion. A control group of dogs received a normal saline bolus followed by saline infusion for the first 24 h of reperfusion. In a subsequent group of dogs treatment consisted of only the 35 mg/kg bolus of SLe(x)-OS to help elucidate the time course of selectin involvement. The saline control group exhibited marked decreases in blood flow in the ischemic-reperfused myocardium, sustained depression of left ventricular function, an average infarct size of 29 +/- 5% of the myocardial area at risk, and excessive polymorphonuclear leukocyte accumulation in the infarcted myocardium after 48 h of reperfusion. Dogs that received a bolus followed by an infusion of SLe(x)-OS exhibited significant preservation of myocardial blood flow and left ventricular function at 4.5 and 48 h of reperfusion, dramatic attenuation (56%) of infarct size (P < 0.05), and a 55% reduction (P < 0.05) in polymorphonuclear leukocyte accumulation compared with the saline group. Interestingly, SLe(x)-OS bolus treatment alone exerted early (i.e., at 4.5 h) cardioprotective effects that waned by 48 h of reperfusion. These results demonstrate that the selectin family of adhesion molecules plays an extended role in myocardial reperfusion injury and is not only involved in the acute phase of this disease process.