Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with both genetic and environmental dynamics contributing to disease progression. Over the last decade, several studies have demonstrated the presence of genomic instability and increased levels of DNA damage in PAH lung vascular cells, which contribute to their pathogenic apoptosis-resistant and proliferating characteristics. In addition, the dysregulated DNA damage response pathways have been indicated as causal factors for the presence of persistent DNA damage. To understand the significant implications of DNA damage and repair in PAH pathogenesis, the current review summarizes the recent advances made in this field. This includes an overview of the observed DNA damage in the nuclear and mitochondrial genome of PAH patients. Next, the irregularities observed in various DNA damage response pathways and their role in accumulating DNA damage, escaping apoptosis, and proliferation under a DNA damaging environment are discussed. Although the current literature establishes the pertinence of DNA damage in PAH, additional studies are required to understand the temporal sequence of the above-mentioned events. Further, an exploration of different types of DNA damage in conjunction with associated impaired DNA damage response in PAH will potentially stimulate early diagnosis of the disease and development of novel therapeutic strategies.

中文翻译：

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肺动脉高压的DNA损伤与修复

肺动脉高压 (PAH) 是一种复杂的多因素疾病，其遗传和环境动力学都有助于疾病进展。在过去的十年中，一些研究表明 PAH 肺血管细胞中存在基因组不稳定性和 DNA 损伤水平增加，这有助于它们的致病性抗凋亡和增殖特性。此外，失调的 DNA 损伤反应途径已被表明是持续性 DNA 损伤存在的原因。为了了解 DNA 损伤和修复在 PAH 发病机制中的重要意义，本综述总结了该领域的最新进展。这包括对 PAH 患者核和线粒体基因组中观察到的 DNA 损伤的概述。下一个，讨论了在各种 DNA 损伤反应途径中观察到的不规则性及其在 DNA 损伤环境下积累 DNA 损伤、逃避细胞凋亡和增殖的作用。尽管目前的文献确定了 PAH 中 DNA 损伤的相关性，但还需要更多的研究来了解上述事件的时间顺序。此外，探索不同类型的 DNA 损伤以及 PAH 中相关的受损 DNA 损伤反应将可能刺激疾病的早期诊断和新治疗策略的开发。需要进一步研究以了解上述事件的时间顺序。此外，探索不同类型的 DNA 损伤以及 PAH 中相关的受损 DNA 损伤反应将可能刺激疾病的早期诊断和新治疗策略的开发。需要进一步研究以了解上述事件的时间顺序。此外，探索不同类型的 DNA 损伤以及 PAH 中相关的受损 DNA 损伤反应将可能刺激疾病的早期诊断和新治疗策略的开发。