{"title":"The role of endothelial shear stress on haemodynamics, inflammation, coagulation and glycocalyx during sepsis.","authors":"Florea Lupu, Gary Kinasewitz, Kenneth Dormer","doi":"10.1111/jcmm.15895","DOIUrl":null,"url":null,"abstract":"<p><p>Sepsis is a multifactorial syndrome primarily determined by the host response to an invading pathogen. It is common, with over 48 million cases worldwide in 2017, and often lethal. The sequence of events in sepsis begins with the damage of endothelium within the microvasculature, as a consequence of the inflammatory and coagulopathic responses to the pathogen that can progress to multiple organ failure and death. Most therapeutic interventions target the inflammation and coagulation pathways that act as an auto-amplified vicious cycle, which, if unchecked can be fatal. Normal blood flow and shear stress acting on a healthy endothelium and intact glycocalyx have anti-inflammatory, anticoagulant and self-repairing effects. During early stages of sepsis, the vascular endothelium and its glycocalyx become dysfunctional, yet they are essential components of resuscitation and recovery from sepsis. The effects of shear forces on sepsis-induced endothelial dysfunction, including inflammation, coagulation, complement activation and microcirculatory breakdown are reviewed. It is suggested that early therapeutic strategies should prioritize on the restoration of shear forces and endothelial function and on the preservation of the endothelial-glycocalyx barrier.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15895","citationCount":"60","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cellular and Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/jcmm.15895","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/9/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 60
Abstract
Sepsis is a multifactorial syndrome primarily determined by the host response to an invading pathogen. It is common, with over 48 million cases worldwide in 2017, and often lethal. The sequence of events in sepsis begins with the damage of endothelium within the microvasculature, as a consequence of the inflammatory and coagulopathic responses to the pathogen that can progress to multiple organ failure and death. Most therapeutic interventions target the inflammation and coagulation pathways that act as an auto-amplified vicious cycle, which, if unchecked can be fatal. Normal blood flow and shear stress acting on a healthy endothelium and intact glycocalyx have anti-inflammatory, anticoagulant and self-repairing effects. During early stages of sepsis, the vascular endothelium and its glycocalyx become dysfunctional, yet they are essential components of resuscitation and recovery from sepsis. The effects of shear forces on sepsis-induced endothelial dysfunction, including inflammation, coagulation, complement activation and microcirculatory breakdown are reviewed. It is suggested that early therapeutic strategies should prioritize on the restoration of shear forces and endothelial function and on the preservation of the endothelial-glycocalyx barrier.
期刊介绍:
Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.