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Anti-Angiogenic VEGF-A isoforms in Peripheral Artery Disease

Dr. Vijay Chaitanya Ganta, Augusta University, USA

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Abstract:
Atherosclerotic occlusions, usually in the lower limbs decreases blood flow resulting in peripheral artery disease (PAD). Restoring blood flow by inducing angiogenesis, a process by which new blood vessels are formed for existing vasculature is critical for the recovery of the PAD patients. However, the molecular processes that regulate ischemic muscle revascularization are not clear. Vascular endothelial growth factor (VEGF)-A is a well-known inducer of angiogenesis. However, therapies that targeted VEGF-A to induce angiogenesis and achieve perfusion recovery in PAD did not have any clinical success. One of the recent discoveries that showed the occurrence of an anti-angiogenic VEGF-A isoform family with the VEGF-A presented the possible reason behind the clinical failure of VEGF-A therapy. My lab focuses on understanding the functional role of these anti-angiogenic VEGF-A isoforms in regulating ischemic muscle perfusion recovery using preclinical PAD models. Existing literature indicates that these anti-angiogenic VEGF-A isoforms block the dominant VEGFR2 signaling pathways in endothelial cells to inhibit angiogenesis. However, our recent studies have shown that these isoforms are agonists of VEGFR2 and inhibitors of VEGFR1 and targeting Anti-angiogenic VEGF-A isoforms enables VEGFR1 activation to promote perfusion recovery in preclinical PAD. These studies present targeting anti-angiogenic VEGF-A isoforms as a potential therapeutic target for PAD.

Meeting ID: 929 9919 2588
Passcode: 631397
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