کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2950087 1577412 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Blockade of Angio-Associated Migratory Cell Protein Inhibits Smooth Muscle Cell Migration and Neointima Formation in Accelerated Atherosclerosis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Blockade of Angio-Associated Migratory Cell Protein Inhibits Smooth Muscle Cell Migration and Neointima Formation in Accelerated Atherosclerosis
چکیده انگلیسی

ObjectivesThe aim of this study was to elucidate the role of angio-associated migratory cell protein (AAMP) for the migration of vascular smooth muscle cells (SMCs) and for the development of neointimal hyperplasia after vascular injury.BackgroundAlthough AAMP has been shown to participate in angiogenesis and cancerogenesis and is predominantly expressed in cells with a migratory phenotype, involvement of AAMP during neointima (NI) formation after arterial injury has not been analyzed previously.MethodsThe AAMP content in SMCs was examined using 2-photon laser-scanning microscopy and subcellular fractioning. Migratory potential of SMCs transiently transfected with AAMP expression vectors, transfected with small interfering ribonucleic acid (siRNA), or treated with antirecombinant angio-associated migratory cell protein–antibody (anti-rAAMP-ab) was examined using transwell migration chamber assays. Expression of AAMP was determined in the atherogenic apolipoprotein E knockout (apoE−/−) mouse model and in the porcine coronary restenosis model by immunohistochemistry and by Western blot. ApoE−/− mice were treated intraperitoneally with anti-rAAMP-ab, and wire-injured carotid arteries were examined.ResultsAngio-associated migratory cell protein is localized in the membrane of SMCs, and its expression is enhanced in NI-derived SMCs. The AAMP overexpression increases, while both treatment with anti-rAAMP-ab and transfection with siRNA decreases SMC migration. Knockdown of AAMP decreases RhoA activity in the membrane fraction of SMCs. The AAMP expression by SMCs is enhanced in both animal models. Anti-rAAMP-ab reduces neointimal SMC density at 1 week and NI formation at 4 weeks in apoE−/− mice without affecting proliferation of SMCs.ConclusionsThese data reveal an important functional role of AAMP in the migration of SMCs, identifying AAMP as a potential target to limit lesion formation after injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the American College of Cardiology - Volume 52, Issue 4, 22 July 2008, Pages 302–311
نویسندگان
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