Palmitate‐Induced Glycosylation of Cyclooxygenase‐2 in Primary Human Vascular Smooth Muscle Cells

Obesity is a major risk factor for cardiovascular health and function. One possible cause of obesity is poor nutrition, including the consumption of diets high in saturated fatty acids. Since vascular inflammation is a key etiological factor in cardiovascular disease, we investigated the effect of saturated fatty acid exposure on the modulation of COX‐2 in primary human male brain and aortic vascular smooth muscle cells. Cells were treated chronically (12 to 18 hr) with vehicle (5% BSA and 0.1% ethanol) or palmitate. Protein levels were assessed via western blotting and light microscopy was used to visualize cell density and morphology. Two distinct bands corresponding to the reported 72 and 74 kDa COX‐2 glycoforms were detected following palmitate treatment. A dose‐dependent increase in both forms was observed with the greatest increase observed in the 74 kDa glycoform (enzymatically active form). Glycosylation inhibition with tunicamycin abolished palmitate‐induced increases in the COX‐2 glycoforms and augmented band density of a lower migrating non‐glycosylated form (64 kDa). Palmitate also increased cell density and altered cell morphology. Although selective COX‐2 inhibition with NS‐398 further enhanced COX‐2 levels in the presence of palmitate, it reversed the palmitate dependent changes in cell density and morphology. In conclusion, this study suggest that palmitate alters COX‐2 function potentially by altering its post‐translation modification in vascular smooth muscle. This potential novel regulation of COX‐2 by saturated fatty acids may contribute as a mechanism in the development of cardiovascular disease in part by altering the structure, function, and health of vascular tissue. Support: University of Arizona Sarver Heart Center