Plasma lipoprotein-associated phospholipase A2 is inversely correlated with proprotein convertase subtilisin-kexin type 9.
OBJECTIVE
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a pro-atherogenic phospholipase A(2), 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-PLA(2) mass.


METHODS
Lp-PLA(2) 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/m(2).


RESULTS
Lp-PLA(2) 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-PLA(2) was inversely related to PCSK9 (r = -0.388, p = 0.004). The Lp-PLA(2)/apolipoprotein B ratio, as a measure of the Lp-PLA(2) content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r = -0.575, p <0.001). The inverse relationships of Lp-PLA(2) (p = 0.023) and the Lp-PLA(2)/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-PLA(2) metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA(2) regulation and vice versa to determine effects of Lp-PLA(2) inhibitors on the PCSK9 pathway.
Department of Endocrinology, University Medical Center Groningen, The Netherlands.
Alexander
A
Constantinides
Paul J W H
PJ
Kappelle
Gilles
G
Lambert
Robin P F
RP
Dullaart
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*
D008078:Cholesterol, LDL; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases