Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

被引：18

作者：

Price, David R. ^{[1
,2
]}

Benedetti, Elisa

Hoffman, Katherine L. ^{[3
]}

Gomez-Escobar, Luis ^{[1
]}

Alvarez-Mulett, Sergio ^{[1
]}

Capili, Allyson ^{[1
]}

Sarwath, Hina ^{[10
]}

Parkhurst, Christopher N. ^{[1
,2
]}

Lafond, Elyse ^{[1
,2
]}

Weidman, Karissa ^{[1
,2
]}

Ravishankar, Arjun ^{[4
]}

Cheong, Jin Gyu ^{[4
]}

Batra, Richa

Buyukozkan, Mustafa

Chetnik, Kelsey

Easthausen, Imaani ^{[3
]}

Schenck, Edward J. ^{[1
,2
]}

Racanelli, Alexandra C. ^{[1
,2
]}

Reed, Hasina Outtz ^{[1
,2
]}

Laurence, Jeffrey ^{[2
,5
]}

Josefowicz, Steven Z. ^{[4
]}

Lief, Lindsay ^{[1
,2
]}

Choi, Mary E. ^{[2
,6
,11
]}

Schmidt, Frank

Borczuk, Alain C.

Choi, Augustine M. K. ^{[1
,2
]}

Krumsiek, Jan ^{[12
]}

Rafii, Shahin ^{[2
,7
,8
,9
,12
]}

机构：

[1] Weill Cornell Med, Div Pulm & Crit Care Med, New York, NY USA

[2] New York Presbyterian Hosp, Inst Computat Biomed, Weill Cornell Med Ctr,Weill Cornell Med, Dept Med, New York, NY USA

[3] Weill Cornell Med, Dept Physiol & Biophys, Div Biostat, New York, NY USA

[4] Weill Cornell Med, Dept Populat Hlth Sci, Lab Epigenet & Immun, New York, NY USA

[5] Weill Cornell Med, Dept Pathol & Lab Med, Div Hematol & Med Oncol, New York, NY USA

[6] Weill Cornell Med, Dept Nephrol & Hypertens, New York, NY USA

[7] Ansary Stem Cell Inst, Weill Cornell Med, New York, NY USA

[8] Weill Cornell Med, Dept Med, Div Regenerat Med, New York, NY USA

[9] Weill Cornell Med, Dept Med, New York, NY USA

[10] New York Presbyterian Hosp, Weill Cornell Med Ctr, Weill Cornell Med Qatar, New York, NY USA

[11] New York Presbyterian, Dept Pathol & Lab Med, Weill Cornell Med, New York, NY USA

[12] Weill Cornell Med, 1305 York Ave, New York, NY 10021 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2022年 / 192卷 / 07期

关键词：

POPULATION; RISK; LUNG; MORTALITY; RELEASE; INJURY;

D O I：

10.1016/j.ajpath.2022.04.002

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)-induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies. (Am J Pathol 2022, 192: 1001-1015; https://doi.org/10.1016/j.ajpath.2022.04.002)

引用

页码：1001 / 1015

页数：15