Highlights
- •A new enzyme-linked immunosorbent assay system for endothelial lipase (EL) was developed.
- •The enzyme-linked immunosorbent assay could detect both full-length and C-terminal fragments of EL (total EL).
- •Total EL mass was inversely correlated with high-density lipoprotein cholesterol in patients with coronary artery disease.
- •Total EL could be a predictor for major cardiovascular events in patient with coronary artery disease.
Background
Endothelial lipase (EL), a regulator of plasma high-density lipoprotein cholesterol
(HDL-C), is secreted as a 68-kDa mature glycoprotein, and then cleaved by proprotein
convertases. However, the clinical significance of the circulating EL fragments remains
unclear.
Objective
The objective of this study was to analyze the impact of serum EL fragments on HDL-C
levels and major adverse cardiovascular events (MACE).
Methods
Using novel monoclonal antibodies (RC3A6) against carboxy-terminal EL protein, we
have established a new enzyme-linked immunosorbent assay (ELISA) system, which can
detect both full-length EL protein (full EL) and carboxy-terminal truncated fragments
(total EL) in serum. The previous sandwich ELISA detected only full EL. The full and
total EL mass were measured in 556 patients with coronary artery disease. Among them,
272 patients who underwent coronary intervention were monitored for 2 years for MACE.
Results
There was a significant correlation between serum full and total EL mass (R = 0.45,
P < .0001). However, the total EL mass showed a stronger inverse correlation with serum
HDL-cholesterol concentration than the full EL mass (R = −0.17 vs −0.02). Kaplan-Meier
analysis documented an association of serum total EL mass and MACE (log-rank P = .037). When an optimal cutoff value was set at 96.23 ng/mL, total EL mass was an
independent prognostic factor for MACE in the Cox proportional hazard model (HR; 1.75,
95% CI; 1.10–2.79, P = .018).
Conclusion
Serum total EL mass could be a predictor for MACE in patients with coronary artery
disease. This novel ELISA will be useful for further clarifying the impact of EL on
HDL metabolism and atherosclerosis.
Keywords
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Article info
Publication history
Published online: July 29, 2019
Accepted:
July 21,
2019
Received:
December 21,
2018
Identification
Copyright
© 2019 Published by Elsevier Inc. on behalf of National Lipid Association.