Changes in plasma factor VIII complex and serum lipid profile during atherogenesis in cynomolgus monkeys.

Abstract

If endothelial injury plays a prominent role in early atherogenesis, the plasma levels of von Willebrand factor (VWF), which is made within and normally released from endothelial cells, might be expected to rise as a marker of the cellular damage. To evaluate this hypothesis, we measured plasma VWF (as VIIIR:Ag), factor VIII:C, and serum lipids serially up to 37 weeks in 29 adult male cynomolgus monkeys on an atherogenic diet. Factor VIII:C peaked at 113% above baseline by week 10 (p less than 0.0001), then fell and remained 53% below baseline (p less than 0.04) during weeks 20 to 37. However, the overall rise in VWF was not significant. In contrast, serum cholesterol continued to rise after week 21. Serum phospholipids (PL), triglycerides (TG), and free fatty acids (FFA) showed a temporal pattern similar to VIII:C. Significant positive correlations with VIII:C were noted for PL (r = 0.59, p = 0.0001) and TG (r = 0.36, p = 0.0096). At autopsy, small to moderately advanced atherosclerotic lesions were distributed throughout the aortas of the majority of the animals. We conclude that changes in plasma VIIIR:Ag do not correlate with atherogenesis in this model. However, the similar course of VIII:C, TG, and PL suggests that these substances may be involved and perhaps interrelated early in atherogenesis.