Deletion of tenascin-C gene exacerbates atherosclerosis and induces intraplaque hemorrhage in Apo-E-deficient mice.

Deletion of tenascin-C gene exacerbates atherosclerosis and induces intraplaque hemorrhage in Apo-E-deficient mice.
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DOI:
10.1016/j.carpath.2011.12.005
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发表时间:
2012-09
影响因子:
3.7
通讯作者:
Sharifi, Behrooz G.
Sharifi, Behrooz G.
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Lai;Wang, Wei;Shah, Prediman K.;Song, Lei;Yang, Mingjie;Sharifi, Behrooz G.

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Tenascin-C (TNC), a matricellular protein, is upregulated in atherosclerotic plaques. We investigated whether the deletion of TNC gene affects the development of atherosclerosis in a murine model. TNC−/−/apo E−/− mice were generated and used for atherosclerosis studies. We compared these results to those observed in control groups of apo E−/− mice. The en face analysis of aortic area showed that the mean aortic lesion area of the double KO mice was significantly higher than control mice at different times after feeding of atherogenic diet; the accumulation of lesional macrophages and lipids were significantly higher, respectively. Analysis of cell adhesion molecules revealed that VCAM-1, but not ICAM-1, was upregulated 1 week after feeding of atherogenic diet in the double KO mouse as compared to apo E−/− mouse. Cell culture studies revealed that the expression of VCAM-1 in endothelial cells isolated from the double KO mouse is more sensitive to the TNFα stimulation than the cells isolated from apo E−/− mice. Cell adhesion studies showed that the adherence of RAW monocytic cells to the endothelial cells was significantly enhanced in the cultured endothelial cells from the TNC gene-deleted cells. Following the prolonged feeding of an atherogenic diet (28–30 weeks), the aortic and carotid atherosclerotic lesions frequently demonstrated large grossly visible areas of intraplaque hemorrhage in the double KO mice compared to control. These data unveil a protective role for TNC in atherosclerosis and suggest that TNC signaling may have the potential to reduce atherosclerosis, in part by modulating VCAM-1 expression.
DOI: 10.1097/00006123-199711000-00007
发表时间: 1997-11-01
期刊: NEUROSURGERY
影响因子: 4.8
作者:
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DOI: 10.1161/01.atv.13.2.197
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发表时间: 2006-12-01
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DOI: 10.1096/fj.05-5131fje
发表时间: 2006-02-01
期刊: FASEB JOURNAL
影响因子: 4.8
作者:
Ballard, Victoria L. T.;Sharma, Arti;Edelberg, Jay M.
通讯作者: Edelberg, Jay M.