BACKGROUND: Discrepancy exists between the potent effects of therapeutic angiogenesis in laboratory animals and the marginal results observed in @entity1 with advanced @entity453 . In vitro and small animal data suggest that angiogenesis may depend on locally available @entity842 (NO), but the impact of @entity409 on therapeutic angiogenesis in the myocardium has been unclear. We compared the effects of clinically applicable angiogenesis methods in @entity1707 in which @entity409 was experimentally induced to that observed in normal @entity1707 . METHODS AND RESULTS: Miniswine were fed either a regular (N=13) or @entity753 diet (N=13) for 20 weeks. @entity753 @entity1707 showed @entity301 on videomicroscopy. Animals from both groups received 100 microg of perivascular sustained-release @entity36030 in the lateral myocardial territory, previously made @entity63 by placement of an ameroid constrictor around the circumflex artery. After 4 weeks of @entity36030 therapy, lateral myocardial perfusion was significantly lower in @entity753 than in normocholesterolemic @entity1707 , both at rest and during pacing (0.44+/-0.04 versus 0.81+/-0.15 mL/min/g at rest, respectively; P=0.006; and 0.50+/-0.06 versus 0.71+/-0.10 mL/min/g during pacing; P=0.02). @entity753 @entity1707 showed no net increase in perfusion from @entity36030 treatment. Endothelial cell density and FGF receptor-1 expression were significantly lower in the lateral territory of @entity753 versus normocholesterolemic animals. CONCLUSIONS: The cardiac angiogenic response to @entity36030 treatment using clinically applicable methods was markedly inhibited in @entity753 @entity1707 with @entity301 . These findings suggest that @entity301 is major obstacle to the efficacy of clinical angiogenesis protocols and constitutes a target toward making angiogenesis more effective in @entity1 with advanced @entity301 .

Inhibition of the cardiac angiogenic response to surgical @entity36030 therapy in a @entity1707 XXXX model.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1707 :: ('9823', 'Species') :: ['swine'] @entity753 :: ('OMIM:143890', 'Disease') :: ['hypercholesterolemic', 'Hypercholesterolemic'] @entity301 :: ('MESH:D003327', 'Disease') :: ['coronary disease', 'coronary endothelial dysfunction'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic'] @entity409 :: ('MESH:D008107', 'Disease') :: ['endothelial dysfunction'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity36030 :: ('397643(Tax:9823)', 'Gene') :: ['FGF-2', 'fibroblast growth factor (FGF)-2'] @entity453 :: ('MESH:D003324', 'Disease') :: ['coronary artery disease']
@entity409 :: (MESH:D008107,Disease) :: ['endothelial dysfunction']
