The Renin-angiotensin System in Acute Respiratory Distress Syndrome
10.13865/j.cnki.cjbmb.2025.02.1431
- VernacularTitle:肾素-血管紧张素系统:急性呼吸窘迫综合征中的生命之舵
- Author:
Yan-Li ZHANG
1
;
Cheng-Yu JIANG
1
Author Information
1. 中国医学科学院基础医学研究所,北京协和医学院基础学院,重大疾病共性机制研究全国重点实验室,北京 100005
- Publication Type:Journal Article
- Keywords:
renin-angiotensin system(RAS);
acute respiratory distress syndrome(ARDS);
severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);
avian influenza virus(AIV)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(4):487-493
- CountryChina
- Language:Chinese
-
Abstract:
Acute respiratory distress syndrome(ARDS)is a severe lung disease characterized by a cyto-kine storm,diffuse alveolar injury,increased pulmonary vascular permeability,and clinical manifesta-tions of acute non-cardiogenic pulmonary edema and refractory hypoxemia(PaO2/FIO2≤300 mm Hg),which ultimately leads to multi-organ failure.The rapid onset,severity,and lack of effective treatments contribute to its high mortality rate,ranging from 30％to 70％,posing a significant public health threat.ARDS can be triggered by various etiologies,including severe infections(e.g.,SARS-CoV,SARS-CoV-2,H5N1)and non-infectious causes.Current treatments are largely non-specific and focus on corticoste-roids,traditional Chinese medicine,nutritional support,and mechanical ventilation.The Berlin criteria(2012)are used for diagnosing ARDS,based on the timing of onset,hypox-emia,pulmonary edema,and associated radiological and physiological disorders.Recent studies sugges-ted that biomarkers could enhance diagnostic sensitivity and specificity.For instance,elevated levels of Angiotensin Ⅱ(Ang Ⅱ)have been linked to the severity and prognosis of critical pneumonia,undersco-ring the importance of the renin-angiotensin system(RAS)in ARDS pathogenesis.A key factor in the progression of ARDS is the disruption of the local RAS within lung tissues.Re-search has shown that activation of the Ang Ⅱ-AT1R axis within the RAS contributes to lung injury.ACE2,a critical negative regulator of RAS,plays an essential role in mitigating lung injury caused by Ang Ⅱ over-production.Downregulation of ACE2 in animal models results in an imbalance in the RAS,leading to acute lung injury.Viral infections,including SARS-CoV,SARS-CoV-2,and avian influenza,as well as expo-sure to certain nanomaterials,can induce ARDS by reducing ACE2 levels,disrupting the RAS balance,particularly through activation of the Ang Ⅱ-AT1R axis,which leads to an increase in Ang Ⅱ.We next discuss the exploration of potential therapeutic strategies involving RAS inhibitors,such as angiotensin receptor blockers(ARBs)and ACE2 supplementation.Studies have demonstrated that ARBs,including losartan,can significantly reduce lung injury and improve survival rates in animal mod-els of ARDS induced by viral infections and other causes.Moreover,recombinant human ACE2(rhACE2)has shown protective effects by lowering Ang Ⅱ levels and alleviating pulmonary damage.Ad-ditionally,we discuss the therapeutic potential of ARBs in treating Multi-Organ Dysfunction Syndrome(MODS),as RAS dysregulation plays a critical role in organ injury.Clinical trials indicate that ARBs can improve outcomes in COVID-19 patients.Despite potential adverse effects such as hypotension and electrolyte imbalance,ARBs remain a promising therapeutic option for both ARDS and MODS.Future studies should focus on further elucida-ting the molecular mechanisms underlying RAS regulation in different etiological contexts and developing personalized treatment strategies to optimize clinical outcomes.Overall,targeting RAS—particularly the Ang Ⅱ-AT1R axis—represents a novel and promising approach for treating ARDS and MODS,offering a valuable therapeutic avenue for critically ill patients.
