研究揭示被SARS-CoV-2感染的恆河猴中血管疾病和血栓形成的原因

研究揭示被SARS-CoV-2感染的恆河猴中血管疾病和血栓形成的原因

作者：

小柯機器人

發布時間：2020/10/12 17:00:00

美國貝斯以色列女執事醫療中心Dan H. Barouch小組揭示被SARS-CoV-2感染的恆河猴中血管疾病和血栓形成的原因。相關論文於2020年10月9日在線發表在《細胞》雜誌上。

研究人員證明了感染SARS-CoV-2的人類和恆河猴的肺組織病理學切片中內皮破壞和血管血栓的形成。為了定義與恆河猴SARS-CoV-2發病機理相關的關鍵分子途徑，研究人員進行了支氣管肺泡灌洗（BAL）和外周血的轉錄組分析以及血清的蛋白質組學分析。研究人員觀察到肺中巨噬細胞浸潤以及巨噬細胞、補體、血小板活化、血栓形成和促炎性標誌物上調，包括C反應蛋白、MX1、IL-6、IL-1、IL-8、TNFα和NF-κB。

 

這些結果提出了一種模型，即炎症和血栓形成途徑之間的關鍵相互作用導致了SARS-CoV-2引發的血管疾病。這些的發現提示了COVID-19的潛在治療靶標。

 

據了解，COVID-19大流行已導致世界各地廣泛的發病和死亡。在人類中，驅動SARS-CoV-2發病機制的臨床特徵包括炎症和血栓形成，但這些過程的機制細節尚待確定。

 

附：英文原文

Title: Vascular Disease and Thrombosis in SARS-CoV-2 Infected Rhesus Macaques

Author: Malika Aid, Kathleen Busman-Sahay, Samuel J. Vidal, Zoltan Maliga, Stephen Bondoc, Carly Starke, Margaret Terry, Connor A. Jacobson, Linda Wrijil, Sarah Ducat, Olga R. Brook, Andrew D. Miller, Maciel Porto, Kathryn L. Pellegrini, Maria Pino, Timothy N. Hoang, Abishek Chandrashekar, Shivani Patel, Kathryn Stephenson, Steven E. Bosinger, Hanne Andersen, Mark G. Lewis, Jonathan L. Hecht, Peter K. Sorger, Amanda J. Martinot, Jacob D. Estes, Dan H. Barouch

Issue&Volume: 2020-10-09

Abstract: The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage (BAL) and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2 induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.

DOI: 10.1016/j.cell.2020.10.005

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31311-8

Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216