Excessive Matrix Metalloproteinase-1 and Hyperactivation of Endothelial Cells Occurred in COVID-19 Patients and Were Associated With the Severity of COVID-19

Author:

Syed Fahim1,Li Wei1,Relich Ryan F2,Russell Patrick M2,Zhang Shanxiang2,Zimmerman Michelle K2,Yu Qigui1

Affiliation:

1. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA

2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

Abstract

Abstract Background Systemic vascular injury occurs in coronavirus disease 2019 (COVID-19) patients; however, the underlying mechanisms remain unknown. Methods To clarify the role of inflammatory factors in COVID-19 vascular injury, we used a multiplex immunoassay to profile 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs). Results COVID-19 patients had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only 1 cytokine, macrophage migration inhibitory factor (MIF), was among these altered analytes, while the rest were chemokines/growth factors. Additionally, only matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. We further studied MMP-1 enzymatic activity and multiple endothelial cell (EC) activation markers (soluble forms of CD146, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) and found that they were highly dysregulated in COVID-19 patients. Conclusions COVID-19 patients have a unique inflammatory profile, and excessive MMP-1 and hyperactivation of ECs are associated with the severity of COVID-19.

Funder

NIH National Institute on Alcohol Abuse and Alcoholism

Bill and Melinda Gates Foundation

Indiana Biobank

Indiana Clinical and Translational Sciences Institute

NIH

National Center for Advancing Translational Sciences

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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