Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation.
Arterioscler Thromb Vasc Biol
; 32(6): 1505-12, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22499993
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 ANDRESULTS:
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 160, 180, 181, LPA, and Lp-PLA2 in plaques. LysoPC 160, 180, 181, LPA, and Lp-PLA2 correlated with interleukin-1ß, interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1ß, 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 160, 180, and 181, 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lisofosfatidilcolinas
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Citocinas
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Estenose das Carótidas
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Mediadores da Inflamação
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1-Alquil-2-acetilglicerofosfocolina Esterase
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Fosfolipases A2
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Placa Aterosclerótica
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Inflamação
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article