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针对肾素-血管紧张素-醛固酮系统预防发育起源性高血压和肾脏疾病。

Targeting the Renin-Angiotensin-Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins.

机构信息

Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.

School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

出版信息

Int J Mol Sci. 2021 Feb 25;22(5):2298. doi: 10.3390/ijms22052298.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6431/7956566/08d97948eac3/ijms-22-02298-g001.jpg

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