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41%, of all deaths in the United States in 1998 (1). As a consequence of atherosclerosis, coronary heart disease (CHD) is the most common cause of cardiovascular morbidity and mortality, with an estimated 12 million people suffering from CHD in the United States alone (1). Elevated total and LDL cholesterol are both accepted primary risk factors for atherosclerosis (1-3). An estimated 101 million United States adults have elevated blood cholesterol ( Ͼ 200 mg/dl) and are candidates for LDL cholesterol lowering through dietary intervention (1, 4, 5). Of these, 41 million are considered high risk, having blood cholesterol greater than 240 mg/dl, and drug therapy is recommended (1, 4, 5).Epidemiological studies have shown that elevated triglycerides and reduced HDL cholesterol are also contributing factors for the development of CHD (2, 3, 6-8). Among the adult United States population, 19% of people have low HDL cholesterol ( Ͻ 40 mg/dl) (3, 9, 10) and 21% have hypertriglyceridemia ( Ͼ 150 mg/dl) (3, 10). Thus, as important as elevated LDL cholesterol is as a risk factor for CHD, it is important to recognize that the most common spectrum of lipid abnormalities is atherogenic dyslipidemia, which is present in 45-50% of men with CHD (11, 12) and includes borderline high-risk LDL cholesterol (e.g., 130-159 mg/dl), elevated triglycerides, small dense LDL particles, and low HDL cholesterol.The HMG-CoA reductase inhibitors (statins) are very effective in lowering LDL cholesterol and somewhat effective in reducing triglycerides, but they have only minimal effects on HDL cholesterol (2, 5, 13-15). Indeed, although numerous clinical trials have demonstrated that LDL cholesterol reduction can significantly reduce CHD risk, a great number of treated subjects who achieve substantial LDL cholesterol reduction still experience a clinical event (2,3,(13)(14)(15)(16)(17)(18). Therefore, with the goal of developAbbreviations: CETP, cholesterol ester transfer protein; CHD, coronary heart disease; ER, endoplasmic reticulum; MTP, microsomal triglyceride transfer protein.

Nerve growth factor (NGF) has previously been shown to increase the rate of adhesion of PC-12 pheochromocytoma cells to cell culture dishes. This increase in the rate of adhesion was postulated to be important in NGF-mediated neurite outgrowth. We now report that epidermal growth factor (EGF) is also able to increase the rate of adhesion of PC-12 cells to cell culture dishes, but does not elicit neurite outgrowth. The dose-response curve for EGF is bell-shaped, in contrast to the more classically shaped dose-response curve obtained with NGF. Tetradecanoyl-phorbol-acetate (TPA), a potent tumor promoter, blocks the EGF-induced increase in adhesion rate of PC-12 cells, but does not alter the NGF-induced increase in adhesion rate. TPA shifts the EGF bindings curve to the right for PC-12 cells, but does not alter maximal EGF binding at saturating concentrations of EGF. The binding of NGF to PC-12 cells is not affected by TPA. NGF-induced neurite formation by PC-12 cells is unaffected by TPA, in contrast to the previously reported delay of neurite outgrowth of serum-deprived neuroblastoma cells and NGF-exposed chick embryonic ganglia cells. NGF and EGF both cause a decrease in the number of short microvilli and an increase in the number of long microvilli on PC-12 cells. TPA blocks the decrease in the number of short microvilli in EGF-treated cells, but not in NGF-treated cells. Long microvilli formation is blocked by TPA in both conditions, suggesting the latter are not involved in the increased adhesion rates.