SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial Cells.
SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial Cells.
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DOI：
10.3390/microorganisms9071438
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发表时间：
2021-07-03
期刊：
影响因子：
4.5
通讯作者：
Caruso A
中科院分区：
文献类型：
--
作者：
Caccuri F;Bugatti A;Zani A;De Palma A;Di Silvestre D;Manocha E;Filippini F;Messali S;Chiodelli P;Campisi G;Fiorentini S;Facchetti F;Mauri P;Caruso A
SARS-CoV-2相关的急性呼吸窘迫综合征（ARDS）和急性肺损伤是严重病毒感染的危及生命的表现。导致呼吸系统并发症的致病机制，如内皮细胞增生，血管生成和血管渗漏仍不清楚。在这项研究中，通过使用免疫荧光检测和原位RNA杂交，我们证明了SARS冠状病毒2感染人原代肺微血管内皮细胞（HL-mECs）的细胞病变的影响和释放的感染性颗粒的情况下，能力。初步数据表明，在没有可检测到的ACE 2表达的情况下，整合素在SARS-CoV-2进入HL-mECs中的作用。感染后，发现HL-mEC释放过多的促炎和促血管生成分子，如通过微阵列分析所评估的。这种条件微环境刺激HL-mECs获得血管生成表型。蛋白质组分析证实了SARS-CoV-2感染的HL-mECs对炎症和血管生成反应的重塑，并强调了抗病毒分子如膜联蛋白A6和MX 1的表达。这些结果支持了SARS-CoV-2感染的HL-mECs在感染早期维持血管功能障碍中的直接作用的假设。病毒-宿主相互作用组的构建将有助于确定COVID-19的潜在治疗靶点，旨在抑制SARS-CoV-2感染后HL-mEC持续的炎症和血管生成。
SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) and acute lung injury are life-threatening manifestations of severe viral infection. The pathogenic mechanisms that lead to respiratory complications, such as endothelialitis, intussusceptive angiogenesis, and vascular leakage remain unclear. In this study, by using an immunofluorescence assay and in situ RNA-hybridization, we demonstrate the capability of SARS-CoV-2 to infect human primary lung microvascular endothelial cells (HL-mECs) in the absence of cytopathic effects and release of infectious particles. Preliminary data point to the role of integrins in SARS-CoV-2 entry into HL-mECs in the absence of detectable ACE2 expression. Following infection, HL-mECs were found to release a plethora of pro-inflammatory and pro-angiogenic molecules, as assessed by microarray analyses. This conditioned microenvironment stimulated HL-mECs to acquire an angiogenic phenotype. Proteome analysis confirmed a remodeling of SARS-CoV-2-infected HL-mECs to inflammatory and angiogenic responses and highlighted the expression of antiviral molecules as annexin A6 and MX1. These results support the hypothesis of a direct role of SARS-CoV-2-infected HL-mECs in sustaining vascular dysfunction during the early phases of infection. The construction of virus-host interactomes will be instrumental to identify potential therapeutic targets for COVID-19 aimed to inhibit HL-mEC-sustained inflammation and angiogenesis upon SARS-CoV-2 infection.
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影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
12.7
作者：
Caruso A;Caccuri F;Bugatti A;Zani A;Vanoni M;Bonfanti P;Cazzaniga ME;Perno CF;Messa C;Alberghina L
通讯作者：
Alberghina L
影响因子：
11.8
作者：
Furukawa, Nathan W;Brooks, John T;Sobel, Jeremy
通讯作者：
Sobel, Jeremy
影响因子：
12.7
作者：
Caruso, A;Rotola, A;Di Luca, D
通讯作者：
Di Luca, D