کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10954067 1097834 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
چکیده انگلیسی
Forces associated with blood flow are crucial not only for blood vessel development but also for regulation of vascular pathology. Although there have been many studies characterizing the responses to mechanical stimuli, molecular mechanisms linking biological responses to mechanical forces remain unclear. Hic-5 (hydrogen peroxide-inducible clone-5) is a focal adhesion adaptor protein proposed as a candidate for a mediator of mechanotransduction. In the present study, we generated Hic-5-deficient mice by targeted mutation. Mice lacking Hic-5 are viable and fertile, and show no obvious histological abnormalities including vasculature. However, after wire injury of the femoral artery in Hic-5 deficient mice, histological recovery of arterial media was delayed due to enhanced apoptosis of vascular wall cells, whereas neointima formation was enhanced. Stretch-induced apoptosis was enhanced in cultured vascular smooth muscle cells (vascular SMCs) from Hic-5 deficient mice. Mechanical stress also induced the alteration of intracellular distribution of vinculin from focal adhesions to the whole cytoplasm in SMCs. Immunoelectron microscopic study of vascular SMCs from a wire-injured artery demonstrated that vinculin was dispersed in the nucleus and the cytoplasm in Hic-5-deficient mice whereas vinculin was localized mainly in the sub-plasma membrane region in wild type mice. Our findings indicate that Hic-5 may serve as a key regulator in mechanosensitive vascular remodeling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 50, Issue 1, January 2011, Pages 77-86
نویسندگان
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