Impact of High Serum Levels of MMP-7, MMP-9, TGF-β and PDGF Macrophage Activation Markers on Severity of COVID-19 in Obese-Diabetic Patients

El-din, Asmaa Nasr; Ata, Kamal Abd El-Sattar Ata; Abdel-Gawad, Abdelhady Ragab; Fahmy, Nahed

doi:10.2147/idr.s329004

Cited by 29 publications

(35 citation statements)

References 34 publications

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“…Therewith, values of MMP-9 strongly positively correlated with transforming growth factor-β (TGF-β) and negatively correlated with the anti-inflammatory ratio IL-10/IL-17 and IL-10/TNF-α (Table 3). This is consistent with MMP-9-related proteolytic cleavage and consecutive activation of latent TGF-β, which could promote epithelial to mesenchymal signal transition and fibrogenesis [33,34].…”

Section: Discussionsupporting

confidence: 81%

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes

Savić¹,

Stevanović²,

Mihajlović³

et al. 2022

Int. J. Med. Sci.

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COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

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Section: Discussionsupporting

confidence: 81%

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes

Savić¹,

Stevanović²,

Mihajlović³

et al. 2022

Int. J. Med. Sci.

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“…Interestingly, recent publications shed new light on the prognostic role of several MMPs accumulation in the plasma of COVID-19 patients. High serum levels of MMP7 and MMP9 and the levels of macrophages activation factors, and severity of COVID-19 in obese-diabetic patients were associated with ARDS in COVID-19 patients with risk factors [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice

Gutman

Aftalion

Melamed

et al. 2022

Viruses

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The COVID-19 pandemic caused by the SARS-CoV-2 infection induced lung inflammation characterized by cytokine storm and fulminant immune response of both resident and migrated immune cells, accelerating alveolar damage. In this work we identified members of the matrix metalloprotease (MMPs) family associated with lung extra-cellular matrix (ECM) destruction using K18-hACE2-transgenic mice (K18-hACE2) infected intranasally with SARS-CoV-2. Five days post infection, the lungs exhibited overall alveolar damage of epithelial cells and massive leukocytes infiltration. A substantial pulmonary increase in MMP8, MMP9, and MMP14 in the lungs post SARS-CoV-2 infection was associated with degradation of ECM components including collagen, laminin, and proteoglycans. The process of tissue damage and ECM degradation during SARS-CoV-2 lung infection is suggested to be associated with activity of members of the MMPs family, which in turn may be used as a therapeutic intervention.

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“…Therefore, inhibiting its signaling might represent a promising target for fortunellin [ 133 ]. Alveolar M2 macrophages produce fibro-proliferative markers, such as MMP7, which promote fibrogenesis, leading to lung stiffening; thus, their elevated expression is more vulnerable to COVID-19 infections [ 134 , 135 ]. Plasma MMP-1 enzymatic activity and plasma levels of MMP-1 and VEGF-A were significantly elevated in critical COVID-19 patients [ 136 ].…”

Section: Discussionmentioning

confidence: 99%