Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2021 Feb 25;22(5):2298. doi: 10.3390/ijms22052298.
The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.
肾素-血管紧张素-醛固酮系统(RAAS)与高血压和肾脏疾病有关。发育中的肾脏可能会受到各种早期生命损伤的影响,这种现象被称为肾脏编程,从而导致成年期的高血压和肾脏疾病。这种理论被称为健康与疾病的发育起源(DOHaD)。相反,早期基于 RAAS 的干预措施可能会通过所谓的重编程来逆转编程过程,从而预防疾病的发生。在当前的综述中,我们主要总结了(1)RAAS 与肾脏编程相关的最新知识;(2)支持异常 RAAS 与肾脏编程背后的其他机制(如氧化应激、一氧化氮缺乏、表观遗传调控和肠道微生物失调)之间联系的现有证据;(3)基于 RAAS 的重编程干预措施如何预防发育起源的高血压和肾脏疾病。为了加速基于 RAAS 的干预措施预防高血压和肾脏疾病的转变,需要更深入地了解 RAAS 在肾脏编程中的作用,以及更注重进一步的临床转化。
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