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- Title
Targeted Imaging of Peripheral Angiogenesis in Type-1 Diabetes Demonstrates Impairment of Alpha-v Integrin Activation Associated with Glycation.
- Authors
Dobrucki, Lawrence W.; Kalinowski, Leszek; Dione, Donald P.; Cline, Gary; Mendizabal, Marivi; Young, Lawrence H.; Sinusas, Albert J.
- Abstract
We have previously assessed temporal changes in angiogenesis in murine model of hindlimb ischemia using 99mTc-labeled RGD peptide NC100692 (692, GE Healthcare) targeted at alpha-v integrin. We hypothesize that 692 imaging could evaluate the role of accumulating advanced glycation endproducts (AGEs) on the impairment of integrin activation and peripheral angiogenesis in type-1 diabetes mellitus (DM). Surgical right femoral artery ligation was performed on wild-type C57BL/6 male non-DM mice (n=8) and DM mice at 2 weeks (n=5) and 6 weeks (n=5) alter STZ treatment (40mg/kg i.p. for 5 days). DM mice demonstrated persistent glycosuria and fasting glycemia (>200 mg/dL). At 7 days post ligation, 692 (2.2±0.6mCi) was injected and 75 min later in vivo microSPECT-CT imaging performed. Blood was collected serially for measurement of glucose and HbAlc an index of AGE accumulation. Alter imaging mice were euthanized and tissue from both distal hindlimbs was excised for gamma well counting of 692 activity, and ischemic to non-ischemic ratio calculated. Glucose levels were chronically elevated ∼3-fold at 2 and 6 wks in the DM mice, resulting in a progressive increase in AGE (wk 2: ∼2-fold, wk 6: ∼2.7-fold). Non-invasive microSPECT-CT 692 imaging and total tissue counts (fig), demonstrated a progressive impairment of alpha-v integrin activation in DM with duration of chronic hyperglycemia. microSPECT-CT imaging of alpha-v integrin provides a novel non-invasive approach for evaluation of angiogenic response to ischemia in DM. The decreased alpha-v integrin activation associated with the duration of hyperglycemia and elevated AGEs in DM may play a role in impaired wound healing in DM patients.
- Subjects
NEOVASCULARIZATION; DIABETES; INTEGRINS; ISCHEMIA; LABORATORY mice; HINDLIMB
- Publication
Diabetes, 2007, Vol 56, pA196
- ISSN
0012-1797
- Publication type
Article