TY - JOUR
T1 - High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans
AU - Birjmohun, Rakesh S.
AU - van Leuven, Sander I.
AU - Levels, Johannes H. M.
AU - van 't Veer, Cornelis
AU - Kuivenhoven, Jan Albert
AU - Meijers, Joost C. M.
AU - Levi, Marcel
AU - Kastelein, John J. P.
AU - van der Poll, Tom
AU - Stroes, Erik S. G.
PY - 2007
Y1 - 2007
N2 - OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge. METHODS AND RESULTS: Thirteen healthy men with genetically determined isolated low HDL cholesterol (averaging 0.7+/-0.1 mmol/L) and 14 age- and body weight-matched healthy men with normal/high HDL cholesterol levels (1.9+/-0.4 mmol/L) were challenged with low-dose endotoxin intravenously (1 ng/kg body weight). The incidence and severity of endotoxin-associated clinical symptoms was increased in the low HDL group. Accordingly, both the inflammatory response (tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8, and monocyte chemoattractant protein-1) as well as thrombin generation (prothrombin activation fragments F(1+2)) were significantly increased in the low HDL group on endotoxin challenge. CONCLUSIONS: Low HDL in healthy males is associated with increased sensitivity toward inflammatory stimuli as reflected by enhanced inflammatory and coagulation responses on endotoxin challenge. These antiinflammatory effects of HDL in humans may lend further support to HDL-increasing interventions, particularly in proinflammatory conditions, such as acute coronary syndromes
AB - OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge. METHODS AND RESULTS: Thirteen healthy men with genetically determined isolated low HDL cholesterol (averaging 0.7+/-0.1 mmol/L) and 14 age- and body weight-matched healthy men with normal/high HDL cholesterol levels (1.9+/-0.4 mmol/L) were challenged with low-dose endotoxin intravenously (1 ng/kg body weight). The incidence and severity of endotoxin-associated clinical symptoms was increased in the low HDL group. Accordingly, both the inflammatory response (tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8, and monocyte chemoattractant protein-1) as well as thrombin generation (prothrombin activation fragments F(1+2)) were significantly increased in the low HDL group on endotoxin challenge. CONCLUSIONS: Low HDL in healthy males is associated with increased sensitivity toward inflammatory stimuli as reflected by enhanced inflammatory and coagulation responses on endotoxin challenge. These antiinflammatory effects of HDL in humans may lend further support to HDL-increasing interventions, particularly in proinflammatory conditions, such as acute coronary syndromes
U2 - https://doi.org/10.1161/ATVBAHA.106.136325
DO - https://doi.org/10.1161/ATVBAHA.106.136325
M3 - Article
C2 - 17303780
SN - 1079-5642
VL - 27
SP - 1153
EP - 1158
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 5
ER -