کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3841364 1247975 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Arterial calcification: a tumor necrosis factor-alpha mediated vascular Wnt-opathy
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
Arterial calcification: a tumor necrosis factor-alpha mediated vascular Wnt-opathy
چکیده انگلیسی

Arterial calcification is common in patients with type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and other chronic inflammatory disorders. Arterial calcification is associated with significant morbidity and increased early mortality. The molecular signature of vascular calcification in diabetes is strikingly similar to that of CKD. Low-grade arterial inflammation is common to both conditions, and increased levels of tumor necrosis factor-alpha (TNF-α) have been reported in both DM and CKD. Recently, we described a novel TNF-α regulated Msx2-Wnt osteogenic program that regulates arterial calcification in an animal model of type 2 DM. TNF-α induces the osteogenic bone morphogenetic protein-2 (BMP-2), Msx2, Wnt3a, and Wnt7a mRNAs and leads to increased aortic calcium accumulation. Treatment with the TNF-α neutralizing antibody infliximab abrogates aortic BMP-2-Msx2-Wnt3a and Wnt7a signaling and attenuates aortic calcium accumulation significantly. Mice with vascular TNF-α augmented by the SM22-TNF-α transgene upregulate the aortic Msx2-Wnt3a/Wnt7a axis. Furthermore, SM22-TNF-αTg;TOPGAL mice exhibit greater β-galactosidase reporter staining versus TOPGAL siblings in the aorta and coronaries, which indicates enhanced mural Wnt signaling in response to TNF-alpha. Thus, inflammatory TNF-α signals promote aortic osteogenic Msx2-Wnt programs in type 2 DM, and arterial calcification in this model is a TNF-α–driven Wnt-opathy. Having established the role of TNF-α in diabetic vascular calcification, an unmet need exists to evaluate the role of TNF-α and Msx2-Wnt signals in CKD-related calcification models. If validated in these models, then these findings will have significant therapeutic applications.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 151, Issue 5, May 2008, Pages 233–239
نویسندگان
,