Abstract 13076: Molecular Imaging of Impaired Angiogenesis in Metabolic Syndrome
Aim: Evaluate the angiogenic response to muscle ischemia in a clinically relevant rat model of peripheral arterial disease (PAD) coupled with metabolic syndrome
Background: PAD afflicts 8 to 12 million Americans and carries a mortality rate of 40%. Most of these patients also harbor metabolic syndrome, which impairs their ability to revascularize ischemic tissues. The JCR rat carries a genetic mutation that mimics the clinical manifestations of metabolic syndrome, including insulin resistance, atherosclerosis, obesity, hyperlipidemia, hyperinsulemia, hypertriglyceridemia, hypercholesterolemia and myocardial infarction. JCR obese animals are homozygous for the mutated gene, while JCR lean animals retain the normal gene and serve as healthy controls. Femoral artery ligation in the JCR rat induces hindlimb ischemia and serves as a model of angiogenic response in metabolic syndrome patients.
Methods: Paramagnetic nanoparticles targeted to the αvβ3-integrin were used to map angiogenesis in vivo with MRI. Molecular imaging of angiogenesis was performed in JCR obese and JCR lean rats following surgical ligation of one femoral artery. Ten days after ligation, rats were imaged on a clinical 3T scanner before and 2 hours after injection of αvβ3-targeted nanoparticles.
Results: The lean animal showed much higher enhancement in the ischemic limb (29.2 ± 6.0%) compared to the control limb (17.5 ± 2.2%, p < 0.01) (Fig. 1), indicating active angiogenesis in response to ligation of the femoral artery. In a dramatic demonstration of the physiological effects of metabolic syndrome, the obese rat showed only low levels of signal enhancement in the ischemic limb (9.1 ± 2.9%) and virtually no enhancement in the control limb (6.3 ± 7.4%, p < 0.05) (Fig. 1).
Conclusions: Molecular imaging with αvβ3-targeted nanoparticles can noninvasively detect angiogenesis in response to hindlimb ischemia and reveals impaired angiogenesis in metabolic syndrome.
- © 2010 by American Heart Association, Inc.