کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5534103 | 1550839 | 2017 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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![عکس صفحه اول مقاله: I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties](/preview/png/5534103.png)
چکیده انگلیسی
Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoEâ/â mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4. The data indicated that I4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I4, at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I4 exerts potent inhibitory effects on atherosclerosis onset and development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 440, 15 January 2017, Pages 80-92
Journal: Molecular and Cellular Endocrinology - Volume 440, 15 January 2017, Pages 80-92
نویسندگان
Lingman Ma, Lifen Qian, Qidi Ying, Yan Zhang, Changlin Zhou, Guanzhong Wu,