کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10750155 | 1050296 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Intimal smooth muscle cells are a source but not a sensor of anti-inflammatory CYP450 derived oxylipins
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کلمات کلیدی
EPAepoxy-octadecenoic aciddihydroxy-docosapentaenoic acidISMCOxylipinPPARMSMCLPSSMCDHET - dhetsEH - SEHArachidonic acid - اسید آراشیدونیکepoxyeicosatrienoic acid - اسید اپوکسی اسیاتریتروئینEicosapentaenoic acid - اسید ایکوزاپنتانوئیکdocosahexaenoic acid - اسید داکوزاگزوائونیکdihydroxy-octadecenoic acid - اسید دی هیدروکسی اکتادیکنیکLinoleic acid - اسید لینولئیکhydroxyeicosatetraenoic acid - اسید هیدروکسی اسیستاترونیکEpOME - اپومEpoxygenase - اپوکسیژنازEET - خوردنDHA - دوکوساهگزائنوئیک اسیدSmooth muscle cell - سلول عضلانی صافHETE - هفتهSoluble epoxide hydrolase - هیدرولاز اپوکسی سدیم حلالPeroxisome proliferator activated receptor - گیرنده فعال فعال پروکسیوم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Vascular pathologies are associated with changes in the presence and expression of morphologically distinct vascular smooth muscle cells. In particular, in complex human vascular lesions and models of disease in pigs and rodents, an intimal smooth muscle cell (iSMC) which exhibits a stable epithelioid or rhomboid phenotype in culture is often found to be present in high numbers, and may represent the reemergence of a distinct developmental vascular smooth muscle cell phenotype. The CYP450-oxylipin - soluble epoxide hydrolase (sEH) pathway is currently of great interest in targeting for cardiovascular disease. sEH inhibitors limit the development of hypertension, diabetes, atherosclerosis and aneurysm formation in animal models. We have investigated the expression of CYP450-oxylipin-sEH pathway enzymes and their metabolites in paired intimal (iSMC) and medial (mSMC) cells isolated from rat aorta. iSMC basally released significantly larger amounts of epoxy-oxylipin CYP450 products from eicosapentaenoic acid > docosahexaenoic acid > arachidonic acid > linoleic acid, and expressed higher levels of CYP2C12, CYP2B1, but not CYP2J mRNA compared to mSMC. When stimulated with the pro-inflammatory TLR4 ligand LPS, epoxy-oxylipin production did not change greatly in iSMC. In contrast, LPS induced epoxy-oxylipin products in mSMC and induced CYP2J4. iSMC and mSMC express sEH which metabolizes primary epoxy-oxylipins to their dihydroxy-counterparts. The sEH inhibitors TPPU or AUDA inhibited LPS-induced NFκB activation and iNOS induction in mSMC, but had no effect on NFκB nuclear localization or inducible nitric oxide synthase in iSMC; effects which were recapitulated in part by addition of authentic epoxy-oxylipins. iSMCs are a rich source but not a sensor of anti-inflammatory epoxy-oxylipins. Complex lesions that contain high levels of iSMCs may be more resistant to the protective effects of sEH inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 774-780
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 774-780
نویسندگان
Scott Thomson, Matthew L. Edin, Fred B. Lih, Michael Davies, Muhammad M. Yaqoob, Bruce D. Hammock, Derek Gilroy, Darryl C. Zeldin, David Bishop-Bailey,