Abstract 216: Angiogenic Factor AGGF1 Promotes Therapeutic Angiogenesis in a Mouse Limb Ischemia Model for Peripheral Arterial Disease
Introduction: Peripheral arterial disease (PAD) is caused by atherosclerosis. PAD is a common disease that affects 12% of the adult population and causes significant morbidity and mortality. The existing treatments for PAD, including pharmacological, interventional and surgical procedures, are not sufficient and many patients are opt for limb amputation. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients.
Hypothesis: In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD.
Methods and Results: We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 (AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice of hindlimb ischemia with injection of the empty vector (control group). The blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration. Four weeks after the injection of DNA, the blood flow was approximately 2.19 fold higher in AGGF1 group than that in control. With the increased blood flow in the AGGF1 group, ambulatory impairement were inhibited compared with the control group. Increased AGGF1 expression decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. CD31-positive capillary vessel density was significantly higher in AGGF1-injected limbs than in empty vector-injected limbs.
Conclusions: These data establish that plasmid DNA-based gene transfer of AGGF1 into mouse skeletal muscles is efficient in increase the expression levels of AGGF1 mRNA and protein. Increased AGGF1 expression increases blood flow by increasing density of CD31-positive vessels and by decreasing necrosis in muscle tissues. These findings suggest that AGGF1 may be used as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.
- © 2012 by American Heart Association, Inc.