Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Medical Faculty, Juraj Dobrila University of Pula, Pula, Croatia.
Bioessays. 2021 Mar;43(3):e2000112. doi: 10.1002/bies.202000112. Epub 2020 Dec 18.
This renin-angiotensin system (RAS) interpretation is focused on differences in tissue dependence on RAS and on the topological hierarchy that allows mediators to act only on downstream tissues. Dependence of tissues on RAS: Tested by expectation maximization clustering of the RNA human tissue expression (https://biogps.org/). ACE and vasoconstrictive AT1R clustered with the prorenin receptor. ACE2 and dilatory MAS1 clustered with nine RAS-related genes, highly expressed in: Liver; Cardiac_Myocytes; Skeletal_Muscle; Uterus; Kidney; Lung; Small_Intestine; Smooth_Muscle. RAS and stress accumulation: While prorenin is active after binding to its receptor, binding of soluble renin increases its enzymatic activity several times. Increased renin secretion multiplies the overall capacity for producing Ang I, leading to hypertension and increased vascular resistance. Coronavirus infection and comorbidities: Cardiorespiratory failure during infection is linked to the previously altered RAS role in lungs and myocardium. Reduced vasodilation by ACE2 lead to vasoconstriction and suboptimal tissue perfusion patterns. Also see the video abstract here https://www.youtube.com/watch?v=Jf0Iped-Mws.
该肾素-血管紧张素系统 (RAS) 解释侧重于 RAS 对组织的依赖性差异，以及允许介质仅在下游组织中发挥作用的拓扑层次结构。组织对 RAS 的依赖性：通过对人类组织表达 RNA 的期望最大化聚类进行测试 (https://biogps.org/)。ACE 和血管收缩性 AT1R 与前肾素受体聚集在一起。ACE2 和扩张性 MAS1 与 9 个与 RAS 相关的基因聚集在一起，这些基因在以下组织中高度表达：肝脏；心肌细胞；骨骼肌；子宫；肾脏；肺；小肠；平滑肌。RAS 和应激积累：前肾素与受体结合后具有活性，而可溶性肾素的结合使其酶活性增加数倍。肾素分泌增加会使 Ang I 的产生总量增加，导致高血压和血管阻力增加。冠状病毒感染和合并症：感染期间的心肺衰竭与肺部和心肌中 RAS 作用先前改变有关。ACE2 导致的血管舒张减少会导致血管收缩和组织灌注模式不佳。也可在此处观看视频摘要 https://www.youtube.com/watch?v=Jf0Iped-Mws。
