Department of Medicine, University of Florida College of Medicine, Gainesville, Florida.
Department of Physiology, University of Florida College of Medicine, Gainesville, Florida.
Am J Physiol Lung Cell Mol Physiol. 2022 Jan 1;322(1):L84-L101. doi: 10.1152/ajplung.00037.2021. Epub 2021 Dec 1.
An often overlooked element of pulmonary vascular disease is time. Cellular responses to time, which are regulated directly by the core circadian clock, have only recently been elucidated. Despite an extensive collection of data regarding the role of rhythmic contribution to disease pathogenesis (such as systemic hypertension, coronary artery, and renal disease), the roles of key circadian transcription factors in pulmonary hypertension remain understudied. This is despite a large degree of overlap in the pulmonary hypertension and circadian rhythm fields, not only including shared signaling pathways, but also cell-specific effects of the core clock that are known to result in both protective and adverse lung vessel changes. Therefore, the goal of this review is to summarize the current dialogue regarding common pathways in circadian biology, with a specific emphasis on its implications in the progression of pulmonary hypertension. In this work, we emphasize specific proteins involved in the regulation of the core molecular clock while noting the circadian cell-specific changes relevant to vascular remodeling. Finally, we apply this knowledge to the optimization of medical therapy, with a focus on sleep hygiene and the role of chronopharmacology in patients with this disease. In dissecting the unique relationship between time and cellular biology, we aim to provide valuable insight into the practical implications of considering time as a therapeutic variable. Armed with this information, physicians will be positioned to more efficiently use the full four dimensions of patient care, resulting in improved morbidity and mortality of pulmonary hypertension patients.
肺部血管疾病的一个常被忽视的因素是时间。细胞对时间的反应直接受到核心生物钟的调节,这一现象直到最近才被阐明。尽管有大量关于节律对疾病发病机制(如系统性高血压、冠状动脉和肾脏疾病)贡献的研究数据,但关键的生物钟转录因子在肺动脉高压中的作用仍未得到充分研究。尽管在肺动脉高压和生物钟节律领域存在很大程度的重叠,不仅包括共享的信号通路,还包括核心时钟对特定细胞的影响,这些影响已知会导致肺部血管的保护性和不利变化。因此,本综述的目的是总结当前关于生物钟生物学共同途径的对话,特别强调其在肺动脉高压进展中的意义。在这项工作中,我们强调了参与核心分子钟调节的特定蛋白质,同时注意到与血管重塑相关的生物钟细胞特异性变化。最后,我们将这方面的知识应用于优化医学治疗,重点关注睡眠卫生以及生物钟药理学在该疾病患者中的作用。通过剖析时间和细胞生物学之间的独特关系,我们旨在为将时间作为治疗变量提供有价值的见解。有了这些信息,医生将能够更有效地利用患者护理的全部四个维度,从而提高肺动脉高压患者的发病率和死亡率。