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      Role of Angiopoietin/Tie2 System in Sepsis: A Potential Therapeutic Target

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          Abstract

          Sepsis is a disorder of host response caused by severe infection that can lead to life-threatening organ dysfunction. There is no specific treatment for sepsis. Although there are many different pathogens that can cause sepsis, endothelial dysfunction is a frequent mechanism resulting in vascular leakage and coagulation problem. Recent studies on the regulatory pathways of vascular endothelium have shown that the disturbance of angiopoietin (Ang) /Tie2 axis can induce endothelial cell activation, which is the core pathogenesis of sepsis. In this review, we aim to discuss the regulation of Ang/Tie2 axis and the biomarkers involved in the context of sepsis. Also, we attempt to explore the prospective and feasibility of Ang/Tie2 axis as a potential target for sepsis intervention to improve clinical outcomes.

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Mervyn Singer, Clifford S Deutschman, Christopher Warren Seymour … (2016)
          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Incidence and outcomes of acute lung injury.

            Gordon D Rubenfeld, Ellen Caldwell, Eve Peabody … (2005)
            Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. Despite recent advances in our understanding of the mechanism and treatment of acute lung injury, its incidence and outcomes in the United States have been unclear. We conducted a prospective, population-based, cohort study in 21 hospitals in and around King County, Washington, from April 1999 through July 2000, using a validated screening protocol to identify patients who met the consensus criteria for acute lung injury. A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older. On the basis of this figure, the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years. The in-hospital mortality rate was 38.5 percent. The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age. Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older (P<0.001). We estimate that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days. Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested. Copyright 2005 Massachusetts Medical Society.
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              Acute Kidney Injury from Sepsis: Current Concepts, Epidemiology, Pathophysiology, Prevention and Treatment

              Sadudee Peerapornratana, Carlos Manrique-Caballero, Hernando Gómez … (2019)
              Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Appl Thromb Hemost
                Journal ID (iso-abbrev): Clin Appl Thromb Hemost
                Journal ID (publisher-id): CAT
                Journal ID (hwp): spcat
                Title: Clinical and Applied Thrombosis/Hemostasis
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Print): 1076-0296
                ISSN (Electronic): 1938-2723
                Publication date (Electronic): 6 March 2024
                Publication date Collection: Jan-Dec 2024
                Volume: 30
                Electronic Location Identifier: 10760296241238010
                Affiliations
                [1 ]Department of Critical Care Medicine, Ringgold 159407, universitythe First Affiliated Hospital of China Medical University; , Shenyang, Liaoning Province, China
                Author notes
                [*]Xu Li, Department of Critical Care Medicine, the First Affiliated Hospital of China Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, People's Republic of China. Email: vincentzh002@ 123456outlook.com
                Author information
                https://orcid.org/0000-0001-6750-9539
                Article
                Publisher ID: 10.1177_10760296241238010
                DOI: 10.1177/10760296241238010
                PMC ID: 10921858
                PubMed ID: 38449088
                SO-VID: a25c1298-fce2-476b-8f27-69a873fd40b9
                Copyright © © The Author(s) 2024
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 16 January 2024
                Date revision received : 21 February 2024
                Date accepted : 22 February 2024
                Funding
                Funded by: National Key Research and Development Program of China, FundRef https://doi.org/10.13039/501100012166;
                Award ID: 2022YFC2304605
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 82272195
                Categories
                Subject: Review
                Custom metadata
                typesetter ts19
                cover-date January-December 2024

                Keywords: sepsis,coagulation,endothelium,angiopoietin,tie2
                Data availability:
                Keywords: sepsis, coagulation, endothelium, angiopoietin, tie2

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