School of Clinical Medicine, Xuzhou Medical University, Xuzhou, 221004, China.
School of Stomatology, Xuzhou Medical University, Xuzhou, 221004, China.
Free Radic Biol Med. 2023 Nov 1;208:846-858. doi: 10.1016/j.freeradbiomed.2023.09.036. Epub 2023 Sep 29.
Cardiovascular diseases (CVDs) are leading causes of global mortality; however, their underlying mechanisms remain unclear. The tumor suppressor factor p53 has been extensively studied for its role in cancer and is also known to play an important role in regulating CVDs. Abnormal p53 expression levels and modifications contribute to the occurrence and development of CVDs. Additionally, mounting evidence underscores the critical involvement of mitochondrial dysfunction in CVDs. Notably, studies indicate that p53 abnormalities directly correlate with mitochondrial dysfunction and may even interact with each other. Encouragingly, small molecule inhibitors targeting p53 have exhibited remarkable effects in animal models of CVDs. Moreover, therapeutic strategies aimed at mitochondrial-related molecules and mitochondrial replacement therapy have demonstrated their advantageous potential. Therefore, targeting p53 or mitochondria holds immense promise as a pioneering therapeutic approach for combating CVDs. In this comprehensive review, we delve into the mechanisms how p53 influences mitochondrial dysfunction, including energy metabolism, mitochondrial oxidative stress, mitochondria-induced apoptosis, mitochondrial autophagy, and mitochondrial dynamics, in various CVDs. Furthermore, we summarize and discuss the potential significance of targeting p53 or mitochondria in the treatment of CVDs.
心血管疾病 (CVDs) 是全球死亡率的主要原因；然而，其潜在机制仍不清楚。肿瘤抑制因子 p53 因其在癌症中的作用而被广泛研究，并且已知其在调节 CVDs 方面也发挥着重要作用。异常的 p53 表达水平和修饰有助于 CVDs 的发生和发展。此外，越来越多的证据强调了线粒体功能障碍在 CVDs 中的关键作用。值得注意的是，研究表明 p53 异常与线粒体功能障碍直接相关，甚至可能相互作用。令人鼓舞的是，针对 p53 的小分子抑制剂在 CVDs 的动物模型中表现出显著的效果。此外，针对线粒体相关分子和线粒体替代治疗的治疗策略已经证明了它们有利的潜力。因此，靶向 p53 或线粒体作为一种治疗 CVDs 的开创性治疗方法具有巨大的潜力。在这篇综合综述中，我们深入探讨了 p53 如何影响线粒体功能障碍的机制，包括能量代谢、线粒体氧化应激、线粒体诱导的细胞凋亡、线粒体自噬和线粒体动力学，以及在各种 CVDs 中的作用。此外，我们总结并讨论了靶向 p53 或线粒体在 CVDs 治疗中的潜在意义。
