Plasma Lipoprotein-associated Phospholipase A₂ Is Inversely Correlated with Proprotein Convertase Subtilisin-kexin Type 9

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• 作者：Alexander Constantinides^a ; Paul J.W.H. Kappelle^a ; Gilles Lambert^b ; ^c ; Robin P.F. Dullaart^a ; ^{r.p.f.dullaart@int.umcg.nl}
• 关键词：Low-density lipoprotein cholesterol ; Lp-PLA2 ; PCSK9
• 刊名：Archives of Medical Research
• 出版年：2012
• 期刊代码：24_01884409
• 类别：med
• 出版时间：January, 2012
• 卷：43
• 期：1
• 页码：11-14
• 文件大小：185 K

摘要

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Background and Aims

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a pro-atherogenic phospholipase A₂, which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA₂ mass.

Methods

Lp-PLA₂ mass (turbidimetric immunoassay), PCSK9 (enzyme-linked immunosorbent assay) and (apo) lipoproteins were measured in 53 nondiabetic subjects (27聽women) with body mass index <30 kg/m².

Results

Lp-PLA₂ and PCSK9 levels were both correlated positively with LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol (r聽= 0.330 to r聽= 0.382, p聽鈮?.02). Remarkably, Lp-PLA₂ was inversely related to PCSK9 (r聽= 鈭?.388, p聽= 0.004). The Lp-PLA₂/apolipoprotein B ratio, as a measure of the Lp-PLA₂ content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r聽= 鈭?.575, p <0.001). The inverse relationships of Lp-PLA₂ (p聽= 0.023) and the Lp-PLA₂/apolipoprotein B ratio (p聽= 0.001) with PCSK9 levels remained significant after controlling for age, gender, triglycerides and HDL cholesterol.

Conclusions

Despite increasing effects on LDL cholesterol, higher PCSK9 levels are unlikely to confer impaired Lp-PLA₂ metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA₂ regulation and vice versa to determine effects of Lp-PLA₂ inhibitors on the PCSK9 pathway.