Evidence Supporting a Key Role of Lp-PLA2-Generated Lysophosphatidylcholine in Human Atherosclerotic Plaque Inflammation.

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title = "Evidence Supporting a Key Role of Lp-PLA2-Generated Lysophosphatidylcholine in Human Atherosclerotic Plaque Inflammation.",
abstract = "OBJECTIVE: To determine whether the level of lysophosphatidylcholine (lysoPC) generated by lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with severity of inflammation in human atherosclerotic plaques. Elevated plasma Lp-PLA2 is associated with increased cardiovascular risk. Lp-PLA2 inhibition reduces atherosclerosis. Lp-PLA2 hydrolyzes low-density lipoprotein-oxidized phospholipids generating lysoPCs. According to in vitro studies, lysoPCs are proinflammatory but the association between their generation and plaque inflammation remains unknown. METHODS AND RESULTS: Inflammatory activity in carotid plaques (162 patients) was determined immunohistochemically and by analyzing cytokines in homogenates (multiplex immunoassay). LysoPCs were quantified using mass spectrometry and Lp-PLA2 and the lysoPC metabolite lysophosphatidic acid (LPA) by ELISA. There was a strong correlation among lysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 in plaques. LysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 correlated with interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, regulated on activation normal T-cell expressed and secreted, and tumor necrosis factor-α in plaques. High lysoPC and Lp-PLA2 correlated with increased plaque macrophages and lipids and with low content of smooth muscle cells, whereas LPA only correlated with plaque macrophages. Lp-PLA2, lysoPC 16:0, 18:0, and 18:1, but not LPA were higher in symptomatic than in asymptomatic plaques. CONCLUSIONS: The associations among Lp-PLA2, lysoPCs, LPA, and proinflammatory cytokines in human plaques suggest that lysoPCs play a key role in plaque inflammation and vulnerability. Our findings support Lp-PLA2 inhibition as a possible strategy for the prevention of cardiovascular disease.",
author = "Isabel Goncalves and Andreas Edsfeldt and Ko, {Na Young} and Helena Grufman and Katarina Berg and Harry Bj{\"o}rkbacka and Mihaela Nitulescu and Ana Persson and Nilsson, {Marie MN} and Cornelia Prehn and Jerzy Adamski and Jan Nilsson",
year = "2012",
doi = "10.1161/ATVBAHA.112.249854",
language = "English",
volume = "32",
pages = "1505",
journal = "Arteriosclerosis, Thrombosis and Vascular Biology",
issn = "1524-4636",
publisher = "Lippincott Williams & Wilkins",
number = "6",