Vascular Protection of Poly(ADP-ribose) Polymerase Inhibitors in the Combination Therapy With Vascular Endothelial Growth Factor Signaling Pathway Inhibitors

聚(ADP-核糖)聚合酶抑制剂与血管内皮生长因子信号通路抑制剂联合治疗的血管保护作用

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Abstract

The Poly(ADP-ribose) polymerase (PARP) family comprises seventeen members that catalyze poly- or mono- adenosine diphosphate (ADP)-ribosylation, a pivotal post-translational modification regulating a wide array of cellular processes, including deoxyribonucleic acid (DNA) repair, apoptosis, protein synthesis, cellular proliferation, and responses to oxidative stress. PARP inhibitors (PARPIs) exhibit selective cytotoxicity in cancers with breast cancer susceptibility gene (BRCA) mutations or defects in homologous recombination. Activation of PARP, indicated by increased poly(ADP-ribose) (PAR) accumulation, is implicated in various disease states such as ischemia-reperfusion injury, vascular disorders, and diabetic complications. Clinically, PARPIs, in combination with anti-angiogenic therapies, not only show efficacy as monotherapies in epithelial ovarian cancer but also mitigate hypertension induced by anti-angiogenic agents. This review consolidates recent advancements in understanding the dual therapeutic potential of PARP inhibition, encompassing both antineoplastic and cardioprotective effects.

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