Impaired revascularization in a mouse model of type 2 diabetes is associated with dysregulation of a complex angiogenic-regulatory network.
OBJECTIVE
Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis.


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.
Schiekofer
Stephan
S
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St, W611 Boston, MA 02118, USA.
Galasso
Gennaro
G
Sato
Kaori
K
Kraus
Benjamin J
BJ
Walsh
Kenneth
K
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004549:Elastin / Q000235:genetics; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020738:Leptin / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D039942:Neuropilin-1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D020738:Leptin; D039942:Neuropilin-1; D004549:Elastin