on May 26, 2005
Published online before print May 26, 2005, doi: 10.1161/01.ATV.0000171994.89106.ca
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Submitted on March 3, 2005
Accepted on May 11, 2005
Impaired Revascularization in a Mouse Model of Type 2 Diabetes Is Associated With Dysregulation of a Complex Angiogenic-Regulatory Network
Stephan Schiekofer ;
From the Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts.
* To whom correspondence should be addressed. E-mail: kxwalsh{at}bu.edu.
Objective--Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis.
Methods and Results--Here it is shown that angiogenic repair of ischemic hindlimbs was impaired in Leprdb/db mice, a leptin receptor-deficient model of diabetes, compared with wild-type (WT) C57BL/6 mice, as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hindlimb cDNA expression profiles were created from adductor muscle of Leprdb/db and WT mice before and after hindlimb ischemia using Affymetrix GeneChip Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis-related proteins were altered in Leprdb/db versus WT mice after ischemic injury. These transcripts included neuropilin-1, vascular endothelial growth factor-A, placental growth factor, elastin, and matrix metalloproteinases implicated in blood vessel growth and maintenance of vessel wall integrity.
Conclusion--These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.
Key words: diabetes • ischemia • angiogenesis • microarrays
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