Targeting Anti-Angiogenic VEGF₁₆₅b-VEGFR1 Signaling Promotes Nitric Oxide Independent Therapeutic Angiogenesis in Preclinical Peripheral Artery Disease Models.

ABSTRACT: Nitric oxide (NO) is the critical regulator of VEGFR2-induced angiogenesis. Neither VEGF-A over-expression nor L-Arginine (NO-precursor) supplementation has been effective in helping patients with Peripheral Artery Disease (PAD) in clinical trials. One incompletely studied reason may be due to the presence of the less characterized anti-angiogenic VEGF-A (VEGF₁₆₅b) isoform. We have recently shown that VEGF₁₆₅b inhibits ischemic angiogenesis by blocking VEGFR1, not VEGFR2 activation. Here we wanted to determine whether VEGF₁₆₅b inhibition using a monoclonal isoform-specific antibody against VEGF₁₆₅b vs. control, improved perfusion recovery in preclinical PAD models that have impaired VEGFR2-NO signaling, including (1) type-2 diabetic model, (2) en

SUBMITTER: Kuppuswamy S 

PROVIDER: S-EPMC9454804 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature