0011 : In early phase of septic shock, O-GlcNAc improves cardiovascular function without modification of autophagic or inflammatory pathways

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• 作者：Marine Ferron¹ ; ^{marine.ferron@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Julien Cadiet¹ ; Valentine Prat¹ ; Angé ; lique Erraud¹ ; Virginie Aillerie¹ ; Mathieu Mevel² ; John Chatham³ ; Bertrand Rozec⁴ ; Benjamin Lauzier¹ ; Chantal Gauthier¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：235
• 全文大小：51 K

文摘

O-GlcNAcylation, a post-translational modification, is the end product of the hexosamine biosynthetic pathway (HBP). Acute septic shock is characterized by a systemic inflammation associated with a cardiovascular dysfunction. The aim of this study was to determine if the increase in total protein OGlcNAcylation at the early phase of septic shock could improve cardiovascular function and the autophagic or inflammatory pathways were involved in this effect.

Methods

To induce an endotoxemic shock, rats (n=6-8) received iv either lipopolysaccharide (LPS, 5 mg/kg) or saline (CTRL). After 1 h, fluid resuscitation (FR, 15 ml/kg of colloid, iv) was associated or not with HBP substrate: glucosamine (GlcN, 180 mg/kg) or an O-GlcNAcase inhibitor (NButGT, 10 mg/kg). Two hours later, echography and mean arterial pressure (MAP) measurement were performed. Then, hearts and blood samples were collected to evaluate biological parameters, inflammation and autophagy.

Results

LPS rats developed an hypotension which was restored by FR, GlcN and NButGT. They have also a systolic dysfunction with a trend toward an improvement by NButGT and GlcN (ejection fraction: CTRL 80±3, LPS 66±3*, LPS-FR 69±2, NButGT 74±2, GlcN 75±2%, *: p<0.01 vs CTRL). Plasmatic troponin T and lactate were significantly increased by 31 and 1.7-fold respectively in LPS rats, and were normalised under NButGT and GlcN conditions. Plasmatic and cardiac cytokines (IL-6 and TNFα) were increased in LPS rats without modification wathever treatments. Autophagic actors like Beclin-1, LC3 and Lamp-2 were not modified by LPS or any treatments.

Conclusion

Our results suggest that O-GlcNAc increase at the early phase of septic shock improves cardiovascular function without involvement of autophagic or inflammatory pathways. We are undergoing to determine which pathways are involved in the beneficial effects induced by the O-GlcNAc increase.

The author hereby declares no conflict of interest