کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5994365 1179828 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin
ترجمه فارسی عنوان
سلول های عضلانی صاف از آنوریسم های آئورت شکمی منحصر به فرد هستند و می توانند به طور مستقل و هم افزایی باعث کاهش الاستین نامحلول
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی

BackgroundThe purpose of this study was to further elucidate the role of the vascular smooth muscle cells (SMCs) in abdominal aortic aneurysm (AAA) disease. We hypothesized that that AAA SMCs are unique and actively participate in the process of degrading the aortic matrix.MethodsWhole-genome expression profiles of SMCs from AAAs, nondilated abdominal aorta (NAA), and carotid endarterectomy (CEA) were compared. We quantified elastolytic activity by culturing SMCs in [3H]elastin-coated plates and measuring solubilized tritium in the media after 7 days. Matrix metalloproteinase (MMP)-2 and MMP-9 production was assessed using real-time polymerase chain reaction, zymography, and Western blotting.ResultsEach SMC type exhibited a unique gene expression pattern. AAA SMCs had greater elastolytic activity than NAA-SMCs (+68%; P < .001) and CEA-SMCs (+45%; P < .001). Zymography showed an increase of active MMP-2 (62 kD) in media from AAA SMCs. AAA SMCs demonstrated twofold greater expression of MMP-2 messenger (m)RNA (P < .05) and 7.3-fold greater MMP-9 expression (P < .01) than NAA-SMCs. Culture with U937 monocytes caused a synergistic increase of elastolysis by AAA SMCs (41%; P < .001) but not NAA-SMCs or CEA-SMCs (P = .99). Coculture with U937 caused a large increase in MMP-9 mRNA in AAA-SMCs and NAA-SMCs (P < .001). MMP-2 mRNA expression was not affected. Western blots of culture media showed a fourfold increase of MMP-9 (92 kD) protein only in AAA-SMCs/U937 but not in NAA-SMCs/U937 (P < .001) and a large increase in active-MMP2 (62 kD), which was less apparent in NAA-SMCs/U937 media (P < .01).ConclusionsAAA-SMCs have a unique gene expression profile and a proelastolytic phenotype that is augmented by macrophages. This may occur by a failure of post-transcriptional control of MMP-9 synthesis.

Clinical RelevanceThe only current therapeutic modalities for treatment of the abdominal aortic aneurysm rely on physical exclusion of the aneurysm-therapies associated with substantial risks and costs. Medical therapies that block the progressive destruction of the aortic wall have great potential to reduce the need for surgical treatment. The experiments in this study demonstrate that the intrinsic smooth muscle cells in the wall of the aneurysmal aorta are uniquely capable of enzymatic destruction of elastin and potentiate the elastolytic capability of the inflammatory cells. Effective therapy for aneurysms may require treatments targeting the dysfunctional activities of the intrinsic smooth muscle cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Vascular Surgery - Volume 60, Issue 4, October 2014, Pages 1033-1042.e5
نویسندگان
, , , , , , , ,