Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock

INTRODUCTION:Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation,...

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Veröffentlicht in:Shock (Augusta, Ga.) Ga.), 2020-10, Vol.54 (4), p.574-582
Hauptverfasser: Clavier, Thomas, Besnier, Emmanuel, Maucotel, Julie, Arabo, Arnaud, Desrues, Laurence, El Amki, Mohamad, Perzo, Nicolas, Richard, Vincent, Tamion, Fabienne, Gandolfo, Pierrick, Dubois, Martine, Castel, Hélène, Compère, Vincent
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container_issue 4
container_start_page 574
container_title Shock (Augusta, Ga.)
container_volume 54
creator Clavier, Thomas
Besnier, Emmanuel
Maucotel, Julie
Arabo, Arnaud
Desrues, Laurence
El Amki, Mohamad
Perzo, Nicolas
Richard, Vincent
Tamion, Fabienne
Gandolfo, Pierrick
Dubois, Martine
Castel, Hélène
Compère, Vincent
description INTRODUCTION:Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock. METHODS:C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated. RESULTS:Urantide treatment improved survival (88.9% vs. 30% on day 6, P 
doi_str_mv 10.1097/SHK.0000000000001448
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The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock. METHODS:C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated. RESULTS:Urantide treatment improved survival (88.9% vs. 30% on day 6, P < 0.05). This was associated with changes in cytokine expressiona decrease in IL-6 (2,485 [2,280–2,751] pg/mL vs. 3,330 [3,119–3,680] pg/mL, P < 0.01) at H6, in IL-3 (1.0 [0.40–2.0] pg/mL vs. 5.8 [3.0–7.7] pg/mL, P < 0.01), and IL-1β (651 [491–1,135] pg/mL vs. 1,601 [906–3,010] pg/mL, P < 0.05) at H12 after LPS administration. Urantide decreased the proportion of cytosolic NF-κB-p65 in liver (1.3 [0.9–1.9] vs. 3.2 [2.3–4], P < 0.01) and kidney (0.3 [0.3–0.4] vs. 0.6 [0.5–1.1], P < 0.01). Urantide improved cardiac function (left ventricular fractional shortening24.8 [21.5–38.9] vs. 12.0 [8.7–17.6] %, P < 0.01 and cardiac output30.3 [25.9–39.8] vs. 15.1 [13.0–16.9] mL/min, P < 0.0001). CONCLUSION:These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.]]></description><identifier>ISSN: 1073-2322</identifier><identifier>EISSN: 1540-0514</identifier><identifier>DOI: 10.1097/SHK.0000000000001448</identifier><identifier>PMID: 31568223</identifier><language>eng</language><publisher>United States: Lippincott Williams &amp; Wilkins</publisher><subject>Life Sciences</subject><ispartof>Shock (Augusta, Ga.), 2020-10, Vol.54 (4), p.574-582</ispartof><rights>Lippincott Williams &amp; Wilkins</rights><rights>2020 by the Shock Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4358-b96462bcac6b0e5e5f7d7f52b8f72517f62438f6be30822f5ae434a94f7f940f3</citedby><cites>FETCH-LOGICAL-c4358-b96462bcac6b0e5e5f7d7f52b8f72517f62438f6be30822f5ae434a94f7f940f3</cites><orcidid>0000-0002-8972-5555 ; 0000-0002-3708-1460</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00024382-202010000-00018$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;NEWS=n&amp;CSC=Y&amp;PAGE=fulltext&amp;D=ovft&amp;AN=00024382-202010000-00018$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>230,314,780,784,885,4609,27924,27925,64666,65461</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31568223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://normandie-univ.hal.science/hal-02335718$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Clavier, Thomas</creatorcontrib><creatorcontrib>Besnier, Emmanuel</creatorcontrib><creatorcontrib>Maucotel, Julie</creatorcontrib><creatorcontrib>Arabo, Arnaud</creatorcontrib><creatorcontrib>Desrues, Laurence</creatorcontrib><creatorcontrib>El Amki, Mohamad</creatorcontrib><creatorcontrib>Perzo, Nicolas</creatorcontrib><creatorcontrib>Richard, Vincent</creatorcontrib><creatorcontrib>Tamion, Fabienne</creatorcontrib><creatorcontrib>Gandolfo, Pierrick</creatorcontrib><creatorcontrib>Dubois, Martine</creatorcontrib><creatorcontrib>Castel, Hélène</creatorcontrib><creatorcontrib>Compère, Vincent</creatorcontrib><title>Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock</title><title>Shock (Augusta, Ga.)</title><addtitle>Shock</addtitle><description><![CDATA[INTRODUCTION:Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock. METHODS:C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated. RESULTS:Urantide treatment improved survival (88.9% vs. 30% on day 6, P < 0.05). This was associated with changes in cytokine expressiona decrease in IL-6 (2,485 [2,280–2,751] pg/mL vs. 3,330 [3,119–3,680] pg/mL, P < 0.01) at H6, in IL-3 (1.0 [0.40–2.0] pg/mL vs. 5.8 [3.0–7.7] pg/mL, P < 0.01), and IL-1β (651 [491–1,135] pg/mL vs. 1,601 [906–3,010] pg/mL, P < 0.05) at H12 after LPS administration. Urantide decreased the proportion of cytosolic NF-κB-p65 in liver (1.3 [0.9–1.9] vs. 3.2 [2.3–4], P < 0.01) and kidney (0.3 [0.3–0.4] vs. 0.6 [0.5–1.1], P < 0.01). Urantide improved cardiac function (left ventricular fractional shortening24.8 [21.5–38.9] vs. 12.0 [8.7–17.6] %, P < 0.01 and cardiac output30.3 [25.9–39.8] vs. 15.1 [13.0–16.9] mL/min, P < 0.0001). CONCLUSION:These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.]]></description><subject>Life Sciences</subject><issn>1073-2322</issn><issn>1540-0514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkt9u0zAUxiMEYmPwBgj5EqRl-G-cXFbVRis6IVF2bTnJsWrq2sVOOvoAvDcOHRPiAnxjy-f3fdY5n4viNcFXBDfy_Xrx8Qr_sQjn9ZPinAiOSywIf5rPWLKSMkrPihcpfcWYctbI58UZI6KqKWXnxY-7qP1ge0DL3T6GAyQ017G3ukM3o-8GG_wlug396PSQa-tjGmBnOzQ_DmFrPaDPkPbBJ7hE2vdo6bsIOk3kGA_2oB2yHs3Q7RgnOBuBQ8Gga9-HIXzPRutN6LYvi2dGuwSvHvaL4u7m-st8Ua4-fVjOZ6uy40zUZdtUvKJtp7uqxSBAGNlLI2hbG0kFkabKDdamaoHh3J4RGjjjuuFGmoZjwy6KdyffjXZqH-1Ox6MK2qrFbKWmO0wZE5LUB5LZtyc2j-XbCGlQO5s6cE57CGNSlDaNrBpRi4zyE9rFkFIE8-hNsJrCUjks9XdYWfbm4YWx3UH_KPqdTgbqE3Af3AAxbd14D1FtQLth8z9v_g8p_vUValpSTDGZROUkrNlPACawCQ</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Clavier, Thomas</creator><creator>Besnier, Emmanuel</creator><creator>Maucotel, Julie</creator><creator>Arabo, Arnaud</creator><creator>Desrues, Laurence</creator><creator>El Amki, Mohamad</creator><creator>Perzo, Nicolas</creator><creator>Richard, Vincent</creator><creator>Tamion, Fabienne</creator><creator>Gandolfo, Pierrick</creator><creator>Dubois, Martine</creator><creator>Castel, Hélène</creator><creator>Compère, Vincent</creator><general>Lippincott Williams &amp; Wilkins</general><general>by the Shock Society</general><general>Lippincott, Williams &amp; Wilkins</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-8972-5555</orcidid><orcidid>https://orcid.org/0000-0002-3708-1460</orcidid></search><sort><creationdate>202010</creationdate><title>Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock</title><author>Clavier, Thomas ; Besnier, Emmanuel ; Maucotel, Julie ; Arabo, Arnaud ; Desrues, Laurence ; El Amki, Mohamad ; Perzo, Nicolas ; Richard, Vincent ; Tamion, Fabienne ; Gandolfo, Pierrick ; Dubois, Martine ; Castel, Hélène ; Compère, Vincent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4358-b96462bcac6b0e5e5f7d7f52b8f72517f62438f6be30822f5ae434a94f7f940f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Life Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clavier, Thomas</creatorcontrib><creatorcontrib>Besnier, Emmanuel</creatorcontrib><creatorcontrib>Maucotel, Julie</creatorcontrib><creatorcontrib>Arabo, Arnaud</creatorcontrib><creatorcontrib>Desrues, Laurence</creatorcontrib><creatorcontrib>El Amki, Mohamad</creatorcontrib><creatorcontrib>Perzo, Nicolas</creatorcontrib><creatorcontrib>Richard, Vincent</creatorcontrib><creatorcontrib>Tamion, Fabienne</creatorcontrib><creatorcontrib>Gandolfo, Pierrick</creatorcontrib><creatorcontrib>Dubois, Martine</creatorcontrib><creatorcontrib>Castel, Hélène</creatorcontrib><creatorcontrib>Compère, Vincent</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Shock (Augusta, Ga.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clavier, Thomas</au><au>Besnier, Emmanuel</au><au>Maucotel, Julie</au><au>Arabo, Arnaud</au><au>Desrues, Laurence</au><au>El Amki, Mohamad</au><au>Perzo, Nicolas</au><au>Richard, Vincent</au><au>Tamion, Fabienne</au><au>Gandolfo, Pierrick</au><au>Dubois, Martine</au><au>Castel, Hélène</au><au>Compère, Vincent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock</atitle><jtitle>Shock (Augusta, Ga.)</jtitle><addtitle>Shock</addtitle><date>2020-10</date><risdate>2020</risdate><volume>54</volume><issue>4</issue><spage>574</spage><epage>582</epage><pages>574-582</pages><issn>1073-2322</issn><eissn>1540-0514</eissn><abstract><![CDATA[INTRODUCTION:Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock. METHODS:C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated. RESULTS:Urantide treatment improved survival (88.9% vs. 30% on day 6, P < 0.05). This was associated with changes in cytokine expressiona decrease in IL-6 (2,485 [2,280–2,751] pg/mL vs. 3,330 [3,119–3,680] pg/mL, P < 0.01) at H6, in IL-3 (1.0 [0.40–2.0] pg/mL vs. 5.8 [3.0–7.7] pg/mL, P < 0.01), and IL-1β (651 [491–1,135] pg/mL vs. 1,601 [906–3,010] pg/mL, P < 0.05) at H12 after LPS administration. Urantide decreased the proportion of cytosolic NF-κB-p65 in liver (1.3 [0.9–1.9] vs. 3.2 [2.3–4], P < 0.01) and kidney (0.3 [0.3–0.4] vs. 0.6 [0.5–1.1], P < 0.01). Urantide improved cardiac function (left ventricular fractional shortening24.8 [21.5–38.9] vs. 12.0 [8.7–17.6] %, P < 0.01 and cardiac output30.3 [25.9–39.8] vs. 15.1 [13.0–16.9] mL/min, P < 0.0001). CONCLUSION:These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.]]></abstract><cop>United States</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>31568223</pmid><doi>10.1097/SHK.0000000000001448</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8972-5555</orcidid><orcidid>https://orcid.org/0000-0002-3708-1460</orcidid></addata></record>
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title Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock
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