| Autor: |
Cescau, Arthur, Caillard, Anais, Sadoune, Malha, Li, Zhenlin, Alexandre, Mebazaa, Vodovar, Nicolas, Charbonnel, Agnès, Lise Samuel, Jane, Logeart, Damien, Cohen Solal, Alain |
| Zdroj: |
Archives of Cardiovascular Diseases Supplements; Apr2015, Vol. 7 Issue 2, p181-181, 1p |
| Abstrakt: |
Introduction QSOX1 was identified as a plasma biomarker of acute heart failure (AHF). QSOX1 being a sulfhydryl oxidase, our aim was to decipher the role of QSOX1 in the heart face to an AHF event. Methods AHF was provoked by IP injections of Isoproterenol (ISO, 300mg/kg/12h) for 2 days in mice (C57Bl/6 J) whereas control (C) received NaCl 9‰. Mice were killed at day 3, after echocardiography. QSOX1 KO (C57Bl/6 J) mice were generated using a QSOX1tm1a embryonic stem cell clone (KOMP). The KO construct contains a promoter-less lacZ gene under the control of the QSOX1 regulatory sequences. The mRNA levels were analyzed by RT-qPCR. The cellular level of oxidative stress was detected by using DHE. Fibrosis was analysed by Sirius red and collagen mRNA. Results At baseline QSOX1 -/- adult mice did not display any cardiac or vascular phenotype. After ISO, lacZ expression dramatically increased in QSOX1 +/- hearts with the strongest β-galactosidase staining in the atria. In mice receiving ISO, a pulmonary congestion, BNP (x2 p<0.001) and CD68 (x3, p<0.001) increases were observed only in QSOX1 -/- , whereas Galectin 3 increased in both groups. After ISO, the severe cardiac dysfunction in QSOX1 -/- mice was associated with signs of enhanced oxidative stress (DHE staining p<0.0001). An early fibrosis was observed by Sirius red analysis and associated with an increase of collagen 1 and 3 mRNAs without difference between WT and QSOX1 -/- mice. Conclusion We provided evidence that the absence of QSOX1 leads to a more serious cardiac dysfunction in response to acute cardiac stress by ISO than in WT counterparts. Hence, our data indicated that QSOX1 protects the heart in response to acute stress. [ABSTRACT FROM AUTHOR] |
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