Tumor necrosis factor-α selectively increases low-density lipoprotein accumulation rate in the artery wall

Tumor necrosis factor-α (TNF), a cytokine produced by activated macrophages, is present in human atheroma and produces the Superoxide anion. In this study we examined the acute effects of TNF on rate of LDL accumulation and lumen volume in the rat carotid artery. Carotid arteries from 3-month old ovariectomized rats were removed and perfused at a constant flow rate of 7ml/min. Rates of fluorescently-labeled LDL (2.5 × 10⁶ MW) accumulation were measured both before and after the addition of TNF using quantitative fluorescence microscopy. TNF perfused at 10ng/ml (n=15 arteries) significantly increased LDL rate of accumulation by 85% (0.13±0.03 mV/min, 0.24±0.06 mV/min; p<0.02). The increase in LDL accumulation rate was seen within 40 minutes of perfusion with TNF. Lumen volume tended to decrease (37.4 ±2.7mV, 33.9 ±2.9mV) with TNF perfusion. In comparison, measurement of fluorescently-labeled dextran (76,000 MW) before and after perfusion with TNF (n=6 arteries) resulted in a minimal decrease of dextran accumulation rate (0.19±0.03mV/min, 0.14±0.01mV/min). In conclusion, TNF selectively increases LDL accumulation rate in perfused arteries. These studies conform to the hypothesis that increased LDL accumulation may result from Superoxide modification of LDL with increased binding of modified LDL to the arterial wall. Current studies investigate the effects of antioxidant enzymes on this process.