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Matrix Metalloproteinases in Health and Disease in the Times of...
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Matrix Metalloproteinases in Health and Disease in the Times of COVID-19

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (20 November 2021) | Viewed by 30638

Special Issue Editors

Dr. Carlos Fernandez-Patron

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Guest Editor
Department of Biochemistry, Mazankowski Alberta Heart Institute, Cardiovascular Research Center, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
Interests: matrix metalloproteinases; cardiovascular; inflammation; lipid metabolism
Dr. Eugenio Hardy

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Guest Editor
Lead, Drug Delivery Lab, Center for Molecular Immunology, Havana, Cuba
Interests: matrix metalloproteinases; cardiovascular; inflammation; lipid metabolism; drug delivery; vaccines; cancer

Special Issue Information

Dear Colleagues,

The pandemic triggered by SARS-CoV-2 (the virus causative of COVID-19) highlights the urgent need to advance our understanding of the interactions between emerging pathogens and their host, as a way to catalyze the design of biomedical and social interventions to mitigate and treat infections. Pathogen–host interactions involve target tissues as well as the immune system and proteinases, enzymes that catalyze the cleavage of specific protein substrates. The role that proteinases play in these interactions is unclear. Matrix metalloproteinases (MMPs) catalyze the cleavage of extracellular matrix components, growth factors, cytokines, and receptors thereof to govern immune responses; cardiovascular function; and the development of cardiovascular diseases, diabetes, cancer, and rheumatoid arthritis (a chronic autoimmune disorder). Individuals with these comorbidities have an increased susceptibility to developing severe COVID-19 illnesses. The roles played by proteinases (MMPs in particular) in the regulation of SARS-CoV-2-host interactions and in increasing the susceptibility to COVID-19 illnesses are largely unknown.

To address this gap in knowledge, this Special Issue aims to be a unique vehicle for exciting mini-reviews and original research articles with the latest advances on the biological roles played by MMPs in health and disease conditions and for contributions proposing provocative new hypotheses at the intersection of COVID-19 and comorbidities that are present in the most severely affected patients with COVID-19.

Dr. Carlos Fernandez-Patron
Dr. Eugenio Hardy
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Proteinases
  • MMPs
  • ADAMs
  • Disease
  • COVID-19
  • Coronavirus

Published Papers (6 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 195 KiB  
Editorial
Matrix Metalloproteinases in Health and Disease in the Times of COVID-19
by Carlos Fernandez-Patron and Eugenio Hardy
Biomolecules 2022, 12(5), 692; https://doi.org/10.3390/biom12050692 - 11 May 2022
Cited by 7 | Viewed by 1433
Abstract
Much has been written about matrix metalloproteinases (MMPs) in health and disease conditions, but their roles in the setting of COVID-19 and associated illnesses remain understudied [...] Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)

Research

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20 pages, 1844 KiB  
Article
Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress
by Pedro V. da Silva-Neto, Valéria B. do Valle, Carlos A. Fuzo, Talita M. Fernandes, Diana M. Toro, Thais F. C. Fraga-Silva, Patrícia A. Basile, Jonatan C. S. de Carvalho, Vinícius E. Pimentel, Malena M. Pérez, Camilla N. S. Oliveira, Lilian C. Rodrigues, Victor A. F. Bastos, Sandra O. C. Tella, Ronaldo B. Martins, Augusto M. Degiovani, Fátima M. Ostini, Marley R. Feitosa, Rogerio S. Parra, Fernando C. Vilar, Gilberto G. Gaspar, José J. R. da Rocha, Omar Feres, Eurico Arruda, Sandra R. Maruyama, Elisa M. S. Russo, Angelina L. Viana, Isabel K. F. M. Santos, Vânia L. D. Bonato, Cristina R. B. Cardoso, Jose E. Tanus-Santos, Eduardo A. Donadi, Lucia H. Faccioli, Marcelo Dias-Baruffi, Ana P. M. Fernandes, Raquel F. Gerlach, Carlos A. Sorgi and on behalf of the IMMUNOCOVID Study Groupadd Show full author list remove Hide full author list
Biomolecules 2022, 12(5), 604; https://doi.org/10.3390/biom12050604 - 19 Apr 2022
Cited by 27 | Viewed by 13454
Abstract
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix [...] Read more.
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)
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Review

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17 pages, 1758 KiB  
Review
Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations
by Alejandro F. Prado, Rose I. M. Batista, Jose E. Tanus-Santos and Raquel F. Gerlach
Biomolecules 2021, 11(4), 585; https://doi.org/10.3390/biom11040585 - 16 Apr 2021
Cited by 33 | Viewed by 4658
Abstract
Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased [...] Read more.
Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased oxidative stress and impaired nitric oxide (NO) bioavailability, which enhance vascular matrix metalloproteinase (MMP) activity. The relationship between NO, MMP and oxidative stress culminating in the vascular alterations of hypertension is examined. While the alterations of hypertension are not fully attributable to these pathophysiological mechanisms, there is strong evidence that such mechanisms play critical roles in increasing vascular MMP expression and activity, thus resulting in abnormal degradation of extracellular matrix components, receptors, peptides, and intracellular proteins involved in the regulation of vascular function and structure. Imbalanced vascular MMP activity promotes vasoconstriction and impairs vasodilation, stimulating vascular smooth muscle cells (VSMC) to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration, which is associated with the deposition of extracellular matrix components. Finally, the protective effects of MMP inhibitors, antioxidants and drugs that enhance vascular NO activity are briefly discussed. Newly emerging therapies that address these essential mechanisms may offer significant advantages to prevent vascular remodeling in hypertensive patients. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)
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16 pages, 2981 KiB  
Review
The Emerging Role of Epigenetic Mechanisms in the Causation of Aberrant MMP Activity during Human Pathologies and the Use of Medicinal Drugs
by Hassan Sarker, Ayman Haimour, Ravneet Toor and Carlos Fernandez-Patron
Biomolecules 2021, 11(4), 578; https://doi.org/10.3390/biom11040578 - 15 Apr 2021
Cited by 13 | Viewed by 2825
Abstract
Matrix metalloproteinases (MMPs) cleave extracellular matrix proteins, growth factors, cytokines, and receptors to influence organ development, architecture, function, and the systemic and cell-specific responses to diseases and pharmacological drugs. Conversely, many diseases (such as atherosclerosis, arthritis, bacterial infections (tuberculosis), viral infections (COVID-19), and [...] Read more.
Matrix metalloproteinases (MMPs) cleave extracellular matrix proteins, growth factors, cytokines, and receptors to influence organ development, architecture, function, and the systemic and cell-specific responses to diseases and pharmacological drugs. Conversely, many diseases (such as atherosclerosis, arthritis, bacterial infections (tuberculosis), viral infections (COVID-19), and cancer), cholesterol-lowering drugs (such as statins), and tetracycline-class antibiotics (such as doxycycline) alter MMP activity through transcriptional, translational, and post-translational mechanisms. In this review, we summarize evidence that the aforementioned diseases and drugs exert significant epigenetic pressure on genes encoding MMPs, tissue inhibitors of MMPs, and factors that transcriptionally regulate the expression of MMPs. Our understanding of human pathologies associated with alterations in the proteolytic activity of MMPs must consider that these pathologies and their medicinal treatments may impose epigenetic pressure on the expression of MMP genes. Whether the epigenetic mechanisms affecting the activity of MMPs can be therapeutically targeted warrants further research. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)
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13 pages, 1158 KiB  
Review
Infarct in the Heart: What’s MMP-9 Got to Do with It?
by Mediha Becirovic-Agic, Upendra Chalise, Michael J. Daseke II, Shelby Konfrst, Jeffrey D. Salomon, Paras K. Mishra and Merry L. Lindsey
Biomolecules 2021, 11(4), 491; https://doi.org/10.3390/biom11040491 - 25 Mar 2021
Cited by 37 | Viewed by 4049
Abstract
Over the past three decades, numerous studies have shown a strong connection between matrix metalloproteinase 9 (MMP-9) levels and myocardial infarction (MI) mortality and left ventricle remodeling and dysfunction. Despite this fact, clinical trials using MMP-9 inhibitors have been disappointing. This review focuses [...] Read more.
Over the past three decades, numerous studies have shown a strong connection between matrix metalloproteinase 9 (MMP-9) levels and myocardial infarction (MI) mortality and left ventricle remodeling and dysfunction. Despite this fact, clinical trials using MMP-9 inhibitors have been disappointing. This review focuses on the roles of MMP-9 in MI wound healing. Infiltrating leukocytes, cardiomyocytes, fibroblasts, and endothelial cells secrete MMP-9 during all phases of cardiac repair. MMP-9 both exacerbates the inflammatory response and aids in inflammation resolution by stimulating the pro-inflammatory to reparative cell transition. In addition, MMP-9 has a dual effect on neovascularization and prevents an overly stiff scar. Here, we review the complex role of MMP-9 in cardiac wound healing, and highlight the importance of targeting MMP-9 only for its detrimental actions. Therefore, delineating signaling pathways downstream of MMP-9 is critical. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)
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Other

20 pages, 1009 KiB  
Essay
Targeting MMP-Regulation of Inflammation to Increase Metabolic Tolerance to COVID-19 Pathologies: A Hypothesis
by Eugenio Hardy and Carlos Fernandez-Patron
Biomolecules 2021, 11(3), 390; https://doi.org/10.3390/biom11030390 - 06 Mar 2021
Cited by 29 | Viewed by 3005
Abstract
Many individuals infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) develop no or only mild symptoms, but some can go on onto develop a spectrum of pathologies including pneumonia, acute respiratory distress syndrome, respiratory failure, systemic inflammation, and multiorgan failure. Many pathogens, [...] Read more.
Many individuals infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) develop no or only mild symptoms, but some can go on onto develop a spectrum of pathologies including pneumonia, acute respiratory distress syndrome, respiratory failure, systemic inflammation, and multiorgan failure. Many pathogens, viral and non-viral, can elicit these pathologies, which justifies reconsidering whether the target of therapeutic approaches to fight pathogen infections should be (a) the pathogen itself, (b) the pathologies elicited by the pathogen interaction with the human host, or (c) a combination of both. While little is known about the immunopathology of SARS-CoV-2, it is well-established that the above-mentioned pathologies are associated with hyper-inflammation, tissue damage, and the perturbation of target organ metabolism. Mounting evidence has shown that these processes are regulated by endoproteinases (particularly, matrix metalloproteinases (MMPs)). Here, we review what is known about the roles played by MMPs in the development of COVID-19 and postulate a mechanism by which MMPs could influence energy metabolism in target organs, such as the lung. Finally, we discuss the suitability of MMPs as therapeutic targets to increase the metabolic tolerance of the host to damage inflicted by the pathogen infection, with a focus on SARS-CoV-2. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease in the Times of COVID-19)
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