Format

Send to

Choose Destination
Circulation. 2007 Sep 11;116(11 Suppl):I31-7.

Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes.

Author information

1
Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02215, USA.

Abstract

BACKGROUND:

Ischemic heart disease is the most common cause of mortality in diabetic patients. Although therapeutic angiogenesis is an attractive option for these patients, they appear to have reduced collateral formation in response to myocardial ischemia. The aims of this study were to establish a large animal model of diabetes and chronic myocardial ischemia, evaluate the effects of diabetes on the angiogenic response, and elucidate the molecular pathways involved.

METHODS AND RESULTS:

Diabetes was induced in male Yucatan miniswine using a pancreatic beta-cell specific toxin, alloxan (150 mg/kg; n=8). Age-matched swine served as controls (n=8). Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Myocardial perfusion and function were assessed at 3 and 7 weeks after ameroid placement using isotope-labeled microspheres. Endothelial cell density and myocardial expression of angiogenic mediators was evaluated. Diabetic animals exhibited significant endothelial dysfunction. Collateral dependent perfusion and LV function were significantly impaired in diabetic animals. Diabetic animals also demonstrated reduced endothelial cell density (173+/-14 versus 234+/-23 cells/hpf, P=0.03). Expression of VEGF, Ang-1, and Tie-2 was reduced, whereas antiangiogenic proteins, angiostatin (4.4+/-0.9-fold increase, P<0.001), and endostatin (2.9+/-0.4-fold increase, P=0.03) were significantly elevated in the diabetic myocardium.

CONCLUSIONS:

Diabetes results in a profound impairment in the myocardial angiogenic response to chronic ischemia. Pro- and antiangiogenic mediators identified in this study offer novel targets for the modulation of the angiogenic response in diabetes.

PMID:
17846323
PMCID:
PMC2723770
DOI:
10.1161/CIRCULATIONAHA.106.680157
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center