- •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.
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.
The objective of this study was to analyze the impact of serum EL fragments on HDL-C levels and major adverse cardiovascular events (MACE).
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.
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).
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.
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Published online: July 29, 2019
Accepted: July 21, 2019
Received: December 21, 2018
© 2019 Published by Elsevier Inc. on behalf of National Lipid Association.