Hypercholesterolemia severely attenuated collateral vessel development in ischemic hindlimbs (angiographic score 0.19 vs 0.35, P<.001), but this was augmented by recombinant human VEGF administration.
Does recombinant human vascular endothelial growth factor improve collateral vessel development in a hypercholesterolemic rabbit model of hindlimb ischemia?
In a rabbit model of hindlimb ischemia, spontaneous hypercholesterolemia severely impairs collateral vessel development, but this deficit can be rescued by the administration of angiogenic cytokines like VEGF.
Absolute Event Rate: 0.19% vs 0.35%
p-value: p=<.001
BACKGROUND: The impact of hyperlipidemia on collateral vessel development in vivo remains enigmatic. We sought to determine the anatomic extent and functional capacity of the collateral bed that develops in response to limb ischemia in a well characterized animal model of spontaneous hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit. We further characterized the impact of exogenous angiogenic cytokine administration on collateral vessel development and function in the same animal model. METHODS AND RESULTS: Weight-matched 6-month-old male homozygous WHHL (n=9) and normal New Zealand White (NZW) (n=9) rabbits underwent surgical resection of one femoral artery. Ten days later, the ischemic hindlimb was evaluated for collateral vessel formation, blood flow, and tissue damage. Collateral vasculature was less extensive among WHHL than NZW, as indicated by a significant reduction in angiographic score (0.19+/-0.02 versus 0.35+/-0.03, P<.001) and capillary density (46.4+/-4.1 versus 78.9+/-4.6/mm2, P<.0002). This was associated with a reduction in calf blood pressure index (9.5+/-3.5% versus 32.8+/-2.8%, P<.0001), arterial blood flow (7.5+/-0.6 versus 13.6+/-0.7 mL/min, P<.0001), and muscle perfusion index (40.1+/-3.2% versus 65.9+/-2.0%, P<.0001) and an increase in muscle necrosis (48.16+/-5.41% versus 25.90+/-3.83% negative 2,3,5-triphenyltetrazolium chloride staining, P<.004). Treatment of WHHL rabbits (n=9) with recombinant human vascular endothelial growth factor produced a statistically significant improvement in all functional as well as anatomic indices of collateral development. CONCLUSIONS: Collateral vessel development associated with hindlimb ischemia in vivo is severely attenuated in an animal model of spontaneous hypercholesterolemia but nevertheless may be augmented by administration of angiogenic cytokines.
Belle et al. (Tue,) conducted a other in Hypercholesterolemia and limb ischemia (n=27). Recombinant human vascular endothelial growth factor vs. Untreated WHHL rabbits and normal NZW rabbits was evaluated on Angiographic score (p=<.001). Hypercholesterolemia severely attenuated collateral vessel development in ischemic hindlimbs (angiographic score 0.19 vs 0.35, P<.001), but this was augmented by recombinant human VEGF administration.