کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2894395 1172434 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses
چکیده انگلیسی

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging cardiovascular risk marker. To explore the biologic role of Lp-PLA2 in atherosclerosis, we examined its expression and contribution to leukocyte activation under proatherogenic conditions.Methods and resultsFollowing the induction of diabetes and hypercholesterolemia in a porcine model, a rapid increase in plasma Lp-PLA2 activity was observed at 1 month. This was accompanied by upregulated Lp-PLA2 mRNA expression by peripheral blood mononuclear cells (PBMC) at 3 months, and elevated Lp-PLA2 mRNA expression in coronary arteries at 6 months. These changes were paralleled by increased inflammatory responses by circulating PBMC (ICAM-1, IL-6), in coronary tissues (ICAM-1, VCAM-1), and the subsequent accumulation of inflammatory cells. In human PBMC, proinflammatory mediators augmented the synthesis and release of functional Lp-PLA2. Furthermore, lysophosphatidylcholine (lysoPC), a product of Lp-PLA2 activity, induced an increase in several inflammatory cytokines (IL-1β, IL-6, TNF-α) in a concentration-dependent manner. In contrast, Lp-PLA2 inhibition (SB677116; 1 μM) abrogated the inflammatory response elicited by oxidized LDL.ConclusionsIn an experimental model of diabetes and hypercholesterolemia, leukocyte activation was associated with augmented Lp-PLA2 expression. In vitro, Lp-PLA2 activity mediated leukocyte activation and inflammatory responses, whereas Lp-PLA2 inhibition abolished inflammatory responses induced by oxidized LDL. Collectively, these observations support a proatherogenic role for Lp-PLA2.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 191, Issue 1, March 2007, Pages 54–62
نویسندگان
, , , , , , , , ,