Your browser doesn't support javascript.
Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.
Price, David R; Benedetti, Elisa; Hoffman, Katherine L; Gomez-Escobar, Luis; Alvarez-Mulett, Sergio; Capili, Allyson; Sarwath, Hina; Parkhurst, Christopher N; Lafond, Elyse; Weidman, Karissa; Ravishankar, Arjun; Cheong, Jin Gyu; Batra, Richa; Büyüközkan, Mustafa; Chetnik, Kelsey; Easthausen, Imaani; Schenck, Edward J; Racanelli, Alexandra C; Outtz Reed, Hasina; Laurence, Jeffrey; Josefowicz, Steven Z; Lief, Lindsay; Choi, Mary E; Schmidt, Frank; Borczuk, Alain C; Choi, Augustine M K; Krumsiek, Jan; Rafii, Shahin.
  • Price DR; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Benedetti E; Institute of Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.
  • Hoffman KL; Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.
  • Gomez-Escobar L; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York.
  • Alvarez-Mulett S; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York.
  • Capili A; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York.
  • Sarwath H; Proteomics Core, Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, Doha, Qatar.
  • Parkhurst CN; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Lafond E; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Weidman K; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Ravishankar A; Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
  • Cheong JG; Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
  • Batra R; Institute of Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.
  • Büyüközkan M; Institute of Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.
  • Chetnik K; Institute of Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.
  • Easthausen I; Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.
  • Schenck EJ; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Racanelli AC; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Outtz Reed H; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Laurence J; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Josefowicz SZ; Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
  • Lief L; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Choi ME; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York; Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Schmidt F; Proteomics Core, Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, Doha, Qatar.
  • Borczuk AC; Department of Pathology and Laboratory Medicine, New York Presbyterian-Weill Cornell Medicine, New York, New York.
  • Choi AMK; Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
  • Krumsiek J; Institute of Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York. Electronic address: jak2043@med.cornell.edu.
  • Rafii S; Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York; Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address: srafii@med.cornell.edu.
Am J Pathol ; 192(7): 1001-1015, 2022 07.
Article in English | MEDLINE | ID: covidwho-1906700
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Angiopoietin-2 / Necroptosis / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Am J Pathol Year: 2022 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Angiopoietin-2 / Necroptosis / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Am J Pathol Year: 2022 Document Type: Article