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

COVID-19 患者存在过多的基质金属蛋白酶-1 和内皮细胞的过度活化,且与 COVID-19 的严重程度相关

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作者:Fahim Syed, Wei Li, Ryan F Relich, Patrick M Russell, Shanxiang Zhang, Michelle K Zimmerman, Qigui Yu

Background

Systemic vascular injury occurs in coronavirus disease 2019 (COVID-19) patients; however, the underlying mechanisms remain unknown.

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.

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.

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