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

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 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 = 0.330 to r = 0.382, p ≤0.02). Remarkably, Lp-PLA2 was inversely related to PCSK9 (r = −0.388, p = 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 = −0.575, p <0.001). The inverse relationships of Lp-PLA2 (p = 0.023) and the Lp-PLA2/apolipoprotein B ratio (p = 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. [Copyright &y& Elsevier]