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 Lepr(db/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 Lepr(db/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 Lepr(db/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. CONCLUSIONS: These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.
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 Lepr(db/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 Lepr(db/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 Lepr(db/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. CONCLUSIONS: These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.
Authors: Xiaochao Wei; Jochen G Schneider; Sherene M Shenouda; Ada Lee; Dwight A Towler; Manu V Chakravarthy; Joseph A Vita; Clay F Semenkovich Journal: J Biol Chem Date: 2010-11-23 Impact factor: 5.157
Authors: Ana Paula Cavalcanti de Sousa; Gardênia Matos Paraguassú; Nara Tayene Teixeira Silveira; José de Souza; Maria Cristina Teixeira Cangussú; Jean Nunes dos Santos; Antonio Luiz Barbosa Pinheiro Journal: Lasers Med Sci Date: 2012-08-25 Impact factor: 3.161
Authors: Ali H Amin; Zakaria Y Abd Elmageed; Devika Nair; Megan I Partyka; Philip J Kadowitz; Souad Belmadani; Khalid Matrougui Journal: Lab Invest Date: 2010-05-03 Impact factor: 5.662
Authors: Jinglian Yan; Guodong Tie; Brian Park; Yagai Yan; Philip T Nowicki; Louis M Messina Journal: J Vasc Surg Date: 2009-10-17 Impact factor: 4.268