The disclosure provides methods and compositions for treating angiogenesis-related disorders, e.g., peripheral arterial disease (PAD), tissue ischemia, etc., using an agent that inhibits C-Jun N-terminal kinase 3 (JNK3) expression and/or activity. Specifically, the disclosure provides methods of treating angiogenesis-related disorders in a subject, the methods comprising administering to the subject a therapeutically effective amount of an agent that inhibits JNK3 expression and/or activity, wherein the agent is an inhibitory nucleic acid, a peptide, or peptide-inhibitor.