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.

中文翻译：

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内皮脂肪酶全长和羧基末端片段的血清浓度预示着冠心病患者未来的心血管风险。

背景

内皮脂酶（EL）是血浆高密度脂蛋白胆固醇（HDL-C）的调节剂，被分泌为68 kDa的成熟糖蛋白，然后被原蛋白转化酶裂解。但是，循环中的EL片段的临床意义仍然不清楚。

客观的

这项研究的目的是分析血清EL片段对HDL-C水平和主要心血管不良事件（MACE）的影响。

方法

使用针对羧基末端EL蛋白的新型单克隆抗体（RC3A6），我们建立了一个新的酶联免疫吸附测定（ELISA）系统，该系统可以检测全长EL蛋白（完整EL）和羧基末端截短的片段（总EL）在血清中。先前的夹心ELISA仅检测到完整的EL。测量了556名冠心病患者的全部EL质量和总EL质量。其中，对接受冠状动脉介入治疗的272例患者进行了2年的MACE监测。

结果

血清充满和总EL量之间存在显着相关性（R = 0.45，P  <.0001）。然而，总EL量与血清HDL-胆固醇浓度之间的反比关系要强于全部EL量（R = -0.17对-0.02）。Kaplan-Meier分析记录了血清总EL量与MACE的相关性（对数秩P  = .037）。当最佳截止值设定为96.23 ng / mL时，在Cox比例风险模型中，总EL质量是MACE的独立预后因素（HR； 1.75，95％CI； 1.10–2.79，P  = .018 ）。

结论

血清总EL量可能是冠心病患者MACE的预测指标。这种新颖的ELISA将有助于进一步阐明EL对HDL代谢和动脉粥样硬化的影响。