دورية أكاديمية
COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction.
| العنوان: | COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction. |
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| المؤلفون: | Queisser KA; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA., Mellema RA; Department of Pathology and., Middleton EA; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA.; Division of General Internal Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA., Portier I; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA., Manne BK; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA., Denorme F; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA., Beswick EJ; Department of Pathology and.; Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA., Rondina MT; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA.; Department of Pathology and.; Division of General Internal Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.; Geriatric Research, Education, and Clinical Center and.; Department of Internal Medicine, George E. Wahlen Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah, USA., Campbell RA; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA., Petrey AC; University of Utah Molecular Medicine Program, Salt Lake City, Utah, USA.; Department of Pathology and.; Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. |
| المصدر: | JCI insight [JCI Insight] 2021 Sep 08; Vol. 6 (17). Date of Electronic Publication: 2021 Sep 08. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | COVID-19/*metabolism , Endothelium, Vascular/*metabolism , Hyaluronic Acid/*metabolism, Aged ; COVID-19/blood ; COVID-19/pathology ; Cytokines/blood ; Endothelium, Vascular/pathology ; Female ; Glycocalyx/metabolism ; Glycocalyx/pathology ; Humans ; Hyaluronan Receptors/metabolism ; Hyaluronic Acid/blood ; Hyaluronoglucosaminidase/blood ; Hyaluronoglucosaminidase/metabolism ; Male ; Middle Aged ; rho-Associated Kinases/metabolism |
| مستخلص: | Vascular injury has emerged as a complication contributing to morbidity in coronavirus disease 2019 (COVID-19). The glycosaminoglycan hyaluronan (HA) is a major component of the glycocalyx, a protective layer of glycoconjugates that lines the vascular lumen and regulates key endothelial cell functions. During critical illness, as in the case of sepsis, enzymes degrade the glycocalyx, releasing fragments with pathologic activities into circulation and thereby exacerbating disease. Here, we analyzed levels of circulating glycosaminoglycans in 46 patients with COVID-19 ranging from moderate to severe clinical severity and measured activities of corresponding degradative enzymes. This report provides evidence that the glycocalyx becomes significantly damaged in patients with COVID-19 and corresponds with severity of disease. Circulating HA fragments and hyaluronidase, 2 signatures of glycocalyx injury, strongly associate with sequential organ failure assessment scores and with increased inflammatory cytokine levels in patients with COVID-19. Pulmonary microvascular endothelial cells exposed to COVID-19 milieu show dysregulated HA biosynthesis and degradation, leading to production of pathological HA fragments that are released into circulation. Finally, we show that HA fragments present at high levels in COVID-19 patient plasma can directly induce endothelial barrier dysfunction in a ROCK- and CD44-dependent manner, indicating a role for HA in the vascular pathology of COVID-19. |
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| معلومات مُعتمدة: | U24 NS107228 United States NS NINDS NIH HHS; K08 HL153953 United States HL NHLBI NIH HHS; UL1 TR002538 United States TR NCATS NIH HHS; R56 AG059877 United States AG NIA NIH HHS; R01 HL130541 United States HL NHLBI NIH HHS; R01 HL142804 United States HL NHLBI NIH HHS; I01 CX001696 United States CX CSRD VA; R00 HL135265 United States HL NHLBI NIH HHS; K01 AG059892 United States AG NIA NIH HHS; R01 AG048022 United States AG NIA NIH HHS |
| فهرسة مساهمة: | Keywords: COVID-19; Extracellular matrix; Glycobiology; Vascular Biology |
| المشرفين على المادة: | 0 (Cytokines) 0 (Hyaluronan Receptors) 9004-61-9 (Hyaluronic Acid) EC 2.7.11.1 (rho-Associated Kinases) EC 3.2.1.35 (Hyaluronoglucosaminidase) |
| تواريخ الأحداث: | Date Created: 20210727 Date Completed: 20210920 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC8492325 |
| DOI: | 10.1172/jci.insight.147472 |
| PMID: | 34314391 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.147472 |