کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2019923 1542249 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel anti-atherogenic role for COX-2—potential mechanism for the cardiovascular side effects of COX-2 inhibitors
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A novel anti-atherogenic role for COX-2—potential mechanism for the cardiovascular side effects of COX-2 inhibitors
چکیده انگلیسی

Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by lipid accumulation, lipoprotein oxidation, and inflammation. Products of the cyclooxygenase (COX) pathway participate in acute and chronic inflammation. The inducible form of COX, COX-2, generates lipid mediators of inflammation that are pro-inflammatory and COX-2-selective inhibitors are potent anti-inflammatory agents. However, clinical data suggest an increased risk of cardiovascular side effects in patients using COX-2-selective inhibitors. In this paper, we sought to determine the effect of COX-2 deficiency on atherosclerosis-related lipoprotein metabolism in mice. We demonstrate that COX-2 deficiency resulted in (i) accumulation of lipids in circulation and liver, (ii) pro-inflammatory properties of HDL as measured by HDL's increased reactive oxygen species (ROS) content, decreased paraoxonase 1 (PON1) activity, decreased serum apoA-1, reduced ability to efflux cholesterol and to prevent LDL oxidizability, and (iii) increased TXB2 in circulation. Moreover, when placed on an atherogenic diet, COX-2 deficiency resulted in (i) increased lipid deposition in the aorta, (ii) a further dramatic imbalance in circulating eicosanoids, i.e. decreased serum PGI2 coupled with increased PGE2 and TXB2, and (iii) a marked elevation of pro-inflammatory cytokines, TNF and IL-6. Our results suggest, for the first time, that COX-2 deficiency contributes to the pro-atherogenic properties of HDL in mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins & Other Lipid Mediators - Volume 84, Issues 1–2, August 2007, Pages 24–33
نویسندگان
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