Metabolites of Arachidonic Acid and Atherosclerosis

526 100191 Metabolites of Arachidonic Acid and Atherosclerosis GUO Ge ZU Lingyun GAO Wei The Department of Cardiology Peking University Third Hospital Beijing 100191 China 1004-3934 2014 05-0526-05 DOI 10. 3969 /j. issn. 1004-3934. 2014. 05. 002 R543. 5 A Abstract As the incidence of cardiovascular disease has increased atherosclerosis has become a focal point of medical research. Recent studies have found that the metabolites of arachidonic acid play an important role in the occurrence development and plaque instability of atherosclerosis and are expected to provide new ideas for the prevention and treatment of atherosclerosis. This paper summarizes the relationship between metabolites of arachidonic acid and atherosclerosis. Key words atherosclerosis arachidonic acid metabolic pathways A 2 atherosclerosis AS AS cyclooxygenase COX lipoxygenase LOX P450 cytochrome P450 AS AS CYP COX LOX 1 hydroxyeicosatetraenoic acid HETE AS CYP ω- 2 AS 1 epoxyeicosatrienoic acids EETs 5 8 11 14-20-HETE 2 AS 1 1987 Email guogeegg@ sina. com Email dr_zly@ 126. com

527 COX PGH 2 H 2 PGD 2 D 2 PGI 2 PGE 2 E 2 TXA 2 A 2 PGDS PGD 2 PGES PGE 2 PGIS PGI 2 TXS TXA 2 LOX FLP 5-5-HPETE 5- HETE 13-HODE 13- LTA 4 A 4 LTA 4 H LTA 4 LTC 4 S LTC 4 LTB 4 B 4 LTC 4 C 4 LTD 4 D 4 LTE 4 E 4 BLT 1 /BLT 2 LTB 4 CysLT 1 /CysLT 2 CYP P450 EETs seh DHETs 1 2 COX COX COX-1 COX-2 COX-1 mpges-1 COX-2 matrix-degrading metalloproteinase MMP AS COX G 2 MMP H 2 PGI 2 E 2 PGE 2 D 2 PGD 2 A 2 thromboxane A 2 TXA 2 PGE 2 /camp 2. 1 PGI 2 TXA 2 AS PGI 2 COX-2 1 PGE 2 MMP PGI 2 1 TXA 2 COX-2 TXA 2 MMP COX-2 /mpges-1 6 PGE 2 PGD 2 PGI 2 TXA 2 κb nuclear factor kappa B NF-κB AS TXA 2 PGI 2 7 PGD 2 15d-PGJ 2 15-deoxy-α12 14-PGJ 2 NF-κB TXA 2 /PGI 2 γ AS AS 3 PGE 2 AS COX-2 / E -1 microsomal PGE synthase-1 AS MMP-2 MMP-9 MMP-2 MMP-9 4 Cipollone 5 COX-2 / mpges- 8 AS -α 2. 2 PGE 2 PGD 2 AS PGD 2 PGE 2

528 9 Cipollone 10 LTB 4 AS AS 60 AS D 3. 2 LTC 4 AS PGD synthase PGDS LTC 4 mpges-1 AS AS mpges-1 PGDS PGE 2 PGD 2 PGE 2 MMP AS LTC 4 LTC 4 COX-2 AS PGDS mpges-1 PGD 2 COX-2 AS mpges-1 PGDS COX-2 61% 14 LTC 4 3 LOX LOX 5-3. 3 12-LOX 15-LOX AS LOX 12-LOX 15-LOX 5-LOX 5-LOX 12-LOX 5- FLAP 15-LOX 12-LOX A 4 leukotreines A 4 LTA 4 LTA 4 12-HETE LTA 4 B 4 LTB 4 15-LOX 15-HETE 13- C 4 LTC 4 AS LTC 4 D 4 E 4 AS AS LTB 4 3. 1 LTB 4 AS LTB 4 AS LTB 4-1 ICAM-1 13- -1 / AS LTB 4 15 15-HETE 5-LOX -1 LTB 4 / LTB 4 CD36 / 4 CYP AS 11 CYP 5-LOX LTB 4 CYP EETs CYP FLAP LTA 4 LTA 4 H Spanbroek 12 AS 4. 1 EETs AS 5-LOX FLAP LTA 4 H EETs 5 6-EET 8 9-EET 11 12-EET 14 5-LOX 15- EET 11 12- EET 14 Qiu 13 15- EET EETs mrna AS EETs AS Ca 2 + K + 5-LOX LTA 4 H K + mrna AS EETs PGI 2 MMP-2 MMP-9 AS 5- EETs EETs LOX 5-LOX E apoe ApoE - / - ApoE - / - LTC 4 LTC 4 mrna 12-LOX 15-LOX 15-HETE HETE ATP

529 16 EETs AS EETs NF-κB AS 11 12- EETs seh AS EET NF-κB EETs -α -1 ICAM-1 17 EETs seh EETs AS EETs 26 soluble epoxide 4. 2 20-HETE hydrolase seh 20-HETE AS dihydroxyeicosatrienoic acids 20-HETE DHETs seh NF-κB ICAM-1-8 AS Ulu 18 ApoE - / - AS AS seh AS 20-HETE 53% EETs /DHETs Han 27 20-HETE AS 11 12-EET /DHETs 14 15-EET / Ⅱ DHETs Wang 19 20-HETE seh 20- AS 33% 39% HETE 72% seh 20-HETE C seh AS EETs 28 20-HETE 29 11 12-EET 14 15-EET 5 AS 5 min 20 Dhanasekaran 21 20 min seh AS left ventricular developed pressure 11 12-EET 14 15-EET seh AS EETs AS 30 CYP AS EETs CYP 22 seh EETs 23 EETs Xu 24 db /db 2 CYP db /db atherosclerosis J Luo 25 seh Ephx2 seh 1 Wong BW Meredith A Lin D et al. The biological role of inflammation in. Can J Cardiol 2012 28 631-641. 2 Capra V B ck M Barbieri SS et al. Eicosanoids and their drugs in cardiovascular diseases focus on atherosclerosis and stroke J. Med Res Rev 2013 33 2 364-438 3 Yuhki K Kashiwagi H Kojima F et al. Roles of prostanoids in the pathogene-

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