Endothelial lipase concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis.
BACKGROUND
Endothelial lipase (EL), a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C) metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans.


RESULTS
Healthy individuals with a family history of premature coronary heart disease (n = 858) were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510), after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC) was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324-617) ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927) ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001). EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each), blood pressure (r = 0.18 and 0.24, p < 0.001 for each), triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004), HDL cholesterol (r = -0.11, p = 0.002; and -0.18, p < 0.001), and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both). EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01) and post-heparin (OR = 2.42, p = 0.003) plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women), and established cardiovascular risk factors.


CONCLUSIONS
We report, to our knowledge for the first time, that human plasma EL concentrations, in both post-heparin and routine pre-heparin plasma, are significantly associated with metabolic syndrome features and with subclinical atherosclerosis. EL may be a pro-atherogenic factor in humans, especially in overweight individuals and those with metabolic syndrome.
Badellino
Karen O
KO
Institute for Translational Medicine and Therapeutics, School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA. kbadelli@nursing.upenn.edu
Wolfe
Megan L
ML
Reilly
Muredach P
MP
Rader
Daniel J
DJ
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000737:chemistry; D008076:Cholesterol, HDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008049:Lipase / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D050177:Overweight; D012307:Risk Factors; D013048:Specimen Handling
D000925:Anticoagulants; D008076:Cholesterol, HDL; D006493:Heparin; C410382:LIPG protein, human; D008049:Lipase