American journal of respiratory cell and molecular biology
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Am. J. Respir. Cell Mol. Biol. · Apr 2021
ReviewPulmonary Endothelial Dysfunction and Thrombotic Complications in COVID-19 Patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new strain of a Coronaviridae virus that presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus, has been recently recognized as the cause of a global pandemic by the World Health Organization, implying a major threat to world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the ACE-2 (angiotensin-converting enzyme 2) receptor, fuses with the cell membrane, enters, and starts its replication process to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. ⋯ The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers, and the development of novel therapies to restore vascular homeostasis and to protect and/or treat coagulation, thrombosis patients. In addition, we review the thrombotic complications recently observed in patients with COVID-19 and its potential threatening sequelae.
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Am. J. Respir. Cell Mol. Biol. · Apr 2021
ReviewTargeting ACE2 for COVID-19 Therapy: Opportunities and Challenges.
The coronavirus disease (COVID-19) pandemic is sweeping the globe. Even with a number of effective vaccines being approved and available to the public, new cases and escalating mortality are climbing every day. ACE2 (angiotensin-converting enzyme 2) is the primary receptor for the COVID-19 causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its complexation with spike proteins plays a crucial role in viral entry into host cells and the subsequent infection. ⋯ In this viewpoint article, we review the current efforts of exploiting ACE2 as a therapeutic target to address this dire medical need. We also provide a holistic view of the pros and cons of each treatment strategy. We highlight the fundamental and translational challenges in moving these research endeavors to clinical applications.
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Am. J. Respir. Cell Mol. Biol. · Aug 2019
ReviewOmics and the Search for Blood Biomarkers in Chronic Obstructive Pulmonary Disease. Insights from COPDGene.
There is an unmet need for blood biomarkers in diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). The search for these biomarkers has been revolutionized by high-throughput sequencing techniques and multiplex platforms that can measure thousands of gene transcripts, proteins, or metabolites. We review COPDGene (Genetic Epidemiology of COPD) project publications that include DNA methylation, transcriptomic, proteomic, and metabolomic blood biomarkers and discuss their impact on COPD. ⋯ Genes, proteins, and metabolite networks are particularly important because the explanatory value of any single molecule is small (1-10%) compared with panels of multiple markers. COPDGene has been a useful resource in the identification and validation of multiple biomarkers for COPD. These biomarkers, either combined in multiple biomarker panels or integrated with other omics data types, may lead to novel diagnostic and prognostic tests for COPD phenotypes and may be relevant for assessing novel therapies.
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Am. J. Respir. Cell Mol. Biol. · Sep 2018
ReviewThe Emerging Role of Neutrophils in Repair after Acute Lung Injury.
Neutrophils are key players in acute lung injury. Once recruited from the circulation, these cells release cytotoxic molecules that lead to tissue disruption, so their blockade has been advocated to prevent lung damage. ⋯ Neutrophils promote epithelial proliferation and are a source of proteases, which are required for the processing of the collagen scar and facilitation of cell migration. This article reviews the effects of neutrophils in repair after acute lung injury, focusing on their role as biovectors for proteases and other molecules involved in tissue remodeling.
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Am. J. Respir. Cell Mol. Biol. · Jul 2018
ReviewAmicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome.
Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. ⋯ Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.