Acute hypertriglyceridaemia in humans increases the triglyceride content and decreases the anti-inflammatory capacity of high density lipoproteins

Introduction: Post-prandial hypertriglyceridaemia is a risk factor for cardiovascular disease, although the underlying mechanisms remain unclear. High density lipoproteins (HDL) have been shown to be atheroprotective, in part through attenuation of vascular inflammation. In this study, the influence of acute hypertriglyceridaemia on the composition and anti-inflammatory properties of HDL was investigated. Methods: Eight fasting healthy male subjects (34 ± 2 years) received 20% Intralipid™ (15 mg/kg/h) or saline, on separate occasions in random order. At baseline and 60 min post-infusion, the total HDL fraction was isolated and its chemical composition determined. HDL were added to TNF-α stimulated human coronary artery endothelial cells and VCAM-1 and ICAM-1 expression was determined by flow cytometry. Results: Serum triglyceride (97.4 ± 8.5 mg/dL baseline, 283.2 ± 35.4 mg/dL post-infusion, p < 0.001) and HDL triglyceride content (3.8 ± 0.5% HDL mass baseline, 5.3 ± 0.9% HDL mass post-infusion, p < 0.05) increased significantly after Intralipid™ infusion. HDL post-Intralipid™ were significantly less anti-inflammatory compared with control (e.g. at 8 μM apoA-I, %VCAM-1 expression 54 ± 5 post-saline, 73 ± 4 post-Intralipid™, p = 0.01; %ICAM-1 expression 94 ± 1 post-saline, 99.4 ± 0.6 post-Intralipid™, p < 0.01). There was also a significant correlation between HDL triglyceride content and VCAM-1 expression (R = 0.70, p = 0.005); as well as between plasma triglyceride levels and both VCAM-1 (R = 0.71, p < 0.005) and ICAM-1 expression (R = 0.80, p < 0.005). Conclusion: Acute hypertriglyceridaemia, simulating the post-prandial state, results in triglyceride-rich HDL with impaired anti-inflammatory capacity.