TY  - JOUR
AU  - Langnau, Carolin
AU  - Rohlfing, Anne-Katrin
AU  - Gekeler, Sarah
AU  - Günter, Manina
AU  - Pöschel, Simone
AU  - Petersen-Uribe, Álvaro
AU  - Jaeger, Philippa
AU  - Avdiu, Alban
AU  - Harm, Tobias
AU  - Kreisselmeier, Klaus-Peter
AU  - Castor, Tatsiana
AU  - Bakchoul, Tamam
AU  - Rath, Dominik
AU  - Gawaz, Meinrad Paul
AU  - Autenrieth, Stella E
AU  - Mueller, Karin Anne Lydia
TI  - Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19.
JO  - Arteriosclerosis, thrombosis, and vascular biology
VL  - 41
IS  - 6
SN  - 1524-4636
CY  - Stanford, Calif.
PB  - HighWire
M1  - DKFZ-2021-00976
SP  - 2080-2096
PY  - 2021
N1  - 2021 Jun;41(6):2080-2096
AB  - Patients with coronary artery disease (CAD) are at increased risk for cardiac death and respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Platelets are crucially involved in pathogenesis of CAD and might also contribute to pathophysiology of SARS-CoV-2 infection. Approach and Results: We enrolled a cohort of 122 participants from February 2020 to July 2020 including 55 patients with preexisting CAD and acute SARS-CoV-2 infection (CAD-SARS-CoV-2positive), 28 patients with CAD and without SARS-CoV-2 (CAD-SARS-CoV-2negative), and 39 healthy controls. Clinical and cardiac examination of the CAD-SARS-CoV-2positive group included blood sampling, echocardiography, and electrocardiography within 24 hours after hospital admission. Phenotyping of platelets was performed by flow cytometry; plasma levels of chemokines were analyzed by ELISA. Respiratory failure of patients was stratified by the Horovitz index as moderately/severely impaired when Horovitz index <200 mm Hg. The clinical end point was defined as Horovitz index <200 mm Hg with subsequent mechanical ventilation within a follow-up of 60 days. CAD-SARS-CoV-2positive patients display a significant enhanced platelet activation and hyper-inflammation early at time of hospital admission. Circulating platelet/leukocyte co-aggregates correlate with plasma levels of cytokines/chemokines like IL (interleukin)-6, CCL2, and CXCL10 as well as activation of platelets is associated with CCL5 and elevation of pulmonary artery pressure. Furthermore, furin is stored and released from activated platelets. High furin plasma levels are associated with poor clinical prognosis in CAD-SARS-CoV-2positive patients.Patients with CAD and SARS-CoV-2 infection exhibit elevated systemic platelet activation and enhanced plasma levels of the subtilisin-like proprotein convertase furin, which may contribute to an unfavorable clinical prognosis.
KW  - coronary artery disease (Other)
KW  - cytokines (Other)
KW  - flow cytometry (Other)
KW  - furin (Other)
KW  - pulmonary artery (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33910372
DO  - DOI:10.1161/ATVBAHA.120.315698
UR  - https://inrepo02.dkfz.de/record/168559
ER  -