Endothelin antagonism and sodium glucose Co-transporter 2 inhibition. A potential combination therapeutic strategy for COVID-19.
Endothelin antagonism and sodium glucose Co-transporter 2 inhibition. A potential combination therapeutic strategy for COVID-19.
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DOI：
10.1016/j.pupt.2021.102035
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发表时间：
2021-08
影响因子：
3.2
通讯作者：
Cheriyan J
中科院分区：
文献类型：
--
作者：
Fisk M;Althage M;Moosmang S;Greasley PJ;Cope AP;Jayne DR;Galloway J;Hall F;Wilkinson IB;Ambery P;Cheriyan J
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的新型冠状病毒2019（COVID-19）感染是一种全球性大流行病，需要采取多方面的方法来应对这一前所未有的健康危机。治疗COVID-19的治疗药物是任何此类管理策略的组成部分，并且对于最有可能患上严重疾病的个体而言，存在大量未满足的治疗需求。本前瞻性综述提供了选择性内皮素-A（ET-A）受体拮抗剂和钠葡萄糖协同转运蛋白-2（SGLT-2）抑制剂联合治疗方案治疗COVID-19的基本原理。内皮素是一种有效的血管收缩剂，具有促炎和动脉粥样硬化作用。它在许多情况下上调，包括急性呼吸窘迫综合征和心血管疾病。内皮素通过血管平滑肌细胞（VSMCs）上的内皮素（ET-A和ET-B）受体介导血管收缩。ET-B受体调节内皮素清除并存在于内皮细胞上，与其在VSMC上的作用相反，其介导血管舒张。因此，选择性内皮素-A（ET-A）受体抑制可能是减轻内皮素损伤作用的最佳方法，并可减少通气-灌注失配和肺部炎症，同时改善肺血流动力学和氧合。SGLT-2抑制可抑制炎性细胞因子，减少高脂血症（如果存在），改善内皮功能、心血管血流动力学和细胞生物能量学。因此，这种联合治疗方法可能对减轻COVID-19的肺部、代谢和心肾表现具有有益作用。鉴于这些药物类别包括分别许可用于治疗心力衰竭、糖尿病和肺动脉高压的药物，因此确定了有关其安全性特征的信息。随机对照临床试验是确定这些药物在COVID-19中的有效性和安全性的最佳方法。
The novel coronavirus 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic that requires a multi-faceted approach to tackle this unprecedent health crisis. Therapeutics to treat COVID-19 are an integral part of any such management strategy and there is a substantial unmet need for treatments for individuals most at risk of severe disease. This perspective review provides rationale of a combined therapeutic regimen of selective endothelin-A (ET-A) receptor antagonism and sodium glucose co-transporter-2 (SGLT-2) inhibition to treat COVID-19. Endothelin is a potent vasoconstrictor with pro-inflammatory and atherosclerotic effects. It is upregulated in a number of conditions including acute respiratory distress syndrome and cardiovascular disease. Endothelin mediates vasocontractility via endothelin (ET-A and ET-B) receptors on vascular smooth muscle cells (VSMCs). ET-B receptors regulate endothelin clearance and are present on endothelial cells, where in contrast to their role on VSMCs, mediate vasodilation. Therefore, selective endothelin-A (ET-A) receptor inhibition is likely the optimal approach to attenuate the injurious effects of endothelin and may reduce ventilation-perfusion mismatch and pulmonary inflammation, whilst improving pulmonary haemodynamics and oxygenation. SGLT-2 inhibition may dampen inflammatory cytokines, reduce hyperglycaemia if present, improve endothelial function, cardiovascular haemodynamics and cellular bioenergetics. This combination therapeutic approach may therefore have beneficial effects to mitigate both the pulmonary, metabolic and cardiorenal manifestations of COVID-19. Given these drug classes include medicines licensed to treat heart failure, diabetes and pulmonary hypertension respectively, information regarding their safety profile is established. Randomised controlled clinical trials are the best way to determine efficacy and safety of these medicines in COVID-19.
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影响因子：
21.1
作者：
Davenport AP;Hyndman KA;Dhaun N;Southan C;Kohan DE;Pollock JS;Pollock DM;Webb DJ;Maguire JJ
通讯作者：
Maguire JJ
影响因子：
19.6
作者：
Chu KH;Tsang WK;Tang CS;Lam MF;Lai FM;To KF;Fung KS;Tang HL;Yan WW;Chan HW;Lai TS;Tong KL;Lai KN
通讯作者：
Lai KN
影响因子：
4
作者：
Castanares, Cristina;Redondo-Horcajo, Mariano;Rodriguez-Pascual, Fernando
通讯作者：
Rodriguez-Pascual, Fernando
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1016/j.trsl.2009.02.007
发表时间：
2009-06
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Comellas AP;Briva A
通讯作者：
Briva A