Tain You-Lin, Hsu Chien-Ning
Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Int J Mol Sci. 2024 Dec 19;25(24):13610. doi: 10.3390/ijms252413610.
The complex relationship between kidney disease and hypertension represents a critical area of research, yet less attention has been devoted to exploring how this connection develops early in life. Various environmental factors during pregnancy and lactation can significantly impact kidney development, potentially leading to kidney programming that results in alterations in both structure and function. This early programming can contribute to adverse long-term kidney outcomes, such as hypertension. In the context of kidney programming, the molecular pathways involved in hypertension are intricate and include epigenetic modifications, oxidative stress, impaired nitric oxide pathway, inappropriate renin-angiotensin system (RAS) activation, disrupted nutrient sensing, gut microbiota dysbiosis, and altered sodium transport. This review examines each of these mechanisms and highlights reprogramming interventions proposed in preclinical studies to prevent hypertension related to kidney programming. Given that reprogramming strategies differ considerably from conventional treatments for hypertension in kidney disease, it is essential to shift focus toward understanding the processes of kidney programming and its role in the development of programmed hypertension.
肾脏疾病与高血压之间的复杂关系是一个关键的研究领域，但对于探索这种联系在生命早期是如何发展的关注较少。妊娠和哺乳期的各种环境因素会显著影响肾脏发育，可能导致肾脏编程，从而导致结构和功能的改变。这种早期编程可能导致不良的长期肾脏结局，如高血压。在肾脏编程的背景下，与高血压相关的分子途径错综复杂，包括表观遗传修饰、氧化应激、一氧化氮途径受损、肾素-血管紧张素系统（RAS）激活不当、营养感知紊乱、肠道微生物群失调以及钠转运改变。本综述探讨了这些机制中的每一种，并强调了临床前研究中提出的预防与肾脏编程相关的高血压的重编程干预措施。鉴于重编程策略与肾脏疾病中高血压的传统治疗方法有很大不同，将重点转向了解肾脏编程过程及其在程序性高血压发展中的作用至关重要。
