کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2893809 1172421 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fatty acids induce apoptosis in human smooth muscle cells depending on chain length, saturation, and duration of exposure
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Fatty acids induce apoptosis in human smooth muscle cells depending on chain length, saturation, and duration of exposure
چکیده انگلیسی

ObjectivePlasma free fatty acid (FFA) concentrations are increased in states of insulin resistance. Therefore, this study evaluated apoptosis and underlying mechanisms induced by selected nutritional FFAs, a defined FFA-mix, and human plasma containing high FFA concentrations in human smooth muscle cells (HSMCs).Research design and methodsHSMCs were incubated (24–72 h) with selected FFAs (100–300 μmol/l), an FFA-mix (palmitic-/stearic-/oleic-/linoleic-/α-linolenic acid = 2.6/1/3.6/9/1; 300–900 μmol/l), or with high FFA-plasma (600 μmol/l) versus respective control cultures. Apoptosis, caspase acitvation, and protein expression were determined by DNA-fragmentation assays, flow cytometry, and Western blots, respectively.ResultsExposure (24 h) of HSMCs to 300 μmol/l stearic-, oleic-, linoleic-, α-linolenic-, and arachidonic acid induced apoptosis, correlating (p < 0.01) with the FFAs’ chain length (r = 0.602) and number of FFA double bonds (r = 0.956). After 48 h, 100 μmol/l of all tested FFAs – including palmitic acid – were already sufficient to trigger HSMCs’ cell death. FFA-exposure resulted in activation of caspases and apoptosis was completely abolished by co-incubation with caspase inhibitors and negatively correlated (p < 0.01) with the base-excision repair protein XRCC1 (r = −0.765) and with c-myc's antagonist mad (r = −0.916), whereas positive correlations (p < 0.01) were found for protein expression of the proto-oncogene c-myc (r = 0.972) and the transcription factor E2F-1 (r = 0.971). Exposure of HSMCs to the defined FFA-mix and to plasma samples from individuals with elevated plasma FFAs supported the results obtained by defined FFA stimulation.ConclusionsSince smooth muscle cells surround the macrophage/foam cell/lipid-laden artheromatous core of atherosclerotic lesions with a protective fibrous cap, their FFA-induced HSMC apoptosis could contribute to progression of atherosclerosis by thinning of the fibrous cap and subsequent plaque destabilization.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 202, Issue 2, February 2009, Pages 351–362
نویسندگان
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