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  1. Article ; Online: Signaling Modulation via Minimal C-Terminal Modifications of Apelin-13.

    Théroux, Léa / Van Den Hauwe, Robin / Trân, Kien / Fournier, Justin / Desgagné, Michael / Meneboo, Nathan / Lavallée, Alexis / Fröhlich, Ulrike / Côté, Jérôme / Hollanders, Charlie / Longpré, Jean-Michel / Murza, Alexandre / Marsault, Eric / Sarret, Philippe / Boudreault, Pierre-Luc / Ballet, Steven

    ACS pharmacology & translational science

    2023  Volume 6, Issue 2, Page(s) 290–305

    Abstract: Apelin is an endogenous peptide that is involved in many diseases such as cardiovascular diseases, obesity, and cancer, which has made it an attractive target for drug discovery. Herein, we explore the penultimate and final sequence positions of [ ... ...

    Abstract Apelin is an endogenous peptide that is involved in many diseases such as cardiovascular diseases, obesity, and cancer, which has made it an attractive target for drug discovery. Herein, we explore the penultimate and final sequence positions of [Pyr
    Language English
    Publishing date 2023-01-26
    Publishing country United States
    Document type Journal Article
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.2c00219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients.

    Coquerel, David / Lamoureux, Julie / Chagnon, Frédéric / Trân, Kien / Sage, Michael / Fortin-Pellerin, Etienne / Delile, Eugénie / Sainsily, Xavier / Fournier, Justin / Dumont, Audrey-Ann / Auger-Messier, Mannix / Sarret, Philippe / Marsault, Eric / Praud, Jean-Paul / Fülöp, Tamàs / Lesur, Olivier

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 22770

    Abstract: Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and ... ...

    Abstract Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.
    MeSH term(s) Aged ; Animals ; Apelin/genetics ; Apelin/metabolism ; Case-Control Studies ; Catecholamines/metabolism ; Enzymes/metabolism ; Feces ; Female ; Follow-Up Studies ; Hemodynamics ; Humans ; Male ; Middle Aged ; Pancreatic Elastase/genetics ; Pancreatic Elastase/metabolism ; Peritonitis/complications ; Prognosis ; Prospective Studies ; Proteolysis ; Sheep ; Shock, Septic/etiology ; Shock, Septic/metabolism ; Shock, Septic/pathology
    Chemical Substances APLN protein, human ; Apelin ; Catecholamines ; Enzymes ; CELA1 protein, human (EC 3.4.21.36) ; Pancreatic Elastase (EC 3.4.21.36)
    Language English
    Publishing date 2021-11-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-02087-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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