Translational studies of lipoprotein-associated phospholipase A₂ in inflammation and atherosclerosis.

Journal of the American College of Cardiology
Jane F FergusonMuredach P Reilly

Abstract

This study sought to examine the role of lipoprotein-associated phospholipase A₂ (Lp-PLA₂/PLA2G7) in human inflammation and coronary atherosclerosis. Lp-PLA₂ has emerged as a potential therapeutic target in coronary heart disease. Data supporting Lp-PLA₂ are indirect and confounded by species differences; whether Lp-PLA₂ is causal in coronary heart disease remains in question. We examined inflammatory regulation of Lp-PLA₂ during experimental endotoxemia in humans, probed the source of Lp-PLA₂ in human leukocytes under inflammatory conditions, and assessed the relationship of variation in PLA2G7, the gene encoding Lp-PLA₂, with coronary artery calcification. In contrast to circulating tumor necrosis factor-alpha and C-reactive protein, blood and monocyte Lp-PLA₂ messenger ribonucleic acid decreased transiently, and plasma Lp-PLA₂ mass declined modestly during endotoxemia. In vitro, Lp-PLA₂ expression increased dramatically during human monocyte to macrophage differentiation and further in inflammatory macrophages and foamlike cells. Despite only a marginal association of single nucleotide polymorphisms in PLA2G7 with Lp-PLA₂ activity or mass, numerous PLA2G7 single nucleotide polymorphisms were associated with coronary artery c...Continue Reading

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Citations

Jun 6, 2012·Journal of Lipid Research·Robert S Rosenson, Diana M Stafforini
Dec 3, 2014·Atherosclerosis·Iolanda Riba-LlenaUNKNOWN ISSYS Study Group
Oct 4, 2016·Journal of the American Heart Association·Samuel Hernandez-AnzaldoCarlos Fernandez-Patron
Feb 21, 2013·Circulation. Cardiovascular Genetics·John J RyanSiddharth K Prakash
May 30, 2019·Medicinal Research Reviews·Fubao HuangJianhua Shen
Nov 6, 2018·Frontiers in Cardiovascular Medicine·Bradley F BaleDavid J Vigerust
Apr 18, 2013·Physiological Genomics·Jaume PadillaR Scott Rector
Dec 18, 2013·European Journal of Clinical Investigation·Ablajan MahmutPatrick Mathieu
Jan 16, 2021·Urology·Jeffrey C BassettChristopher S Saigal

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