Abstract 15428: Qsox1 Has a Protective Role in the Myocardium Face to Acute Stress
Introduction: QSOX1 was identified as a plasma biomarker of acute heart failure (AHF). As QSOX1 is a sulfhydryl oxidase, we hypothesized that QSOX1 has a protective role in the heart face during AHF.
Methods: AHF was provoked by IP injections of Isoproterenol (ISO, 300 mg/kg/12h) for 2 days in mice (Balb-C or C57Bl/6 J) whereas control (C) received NaCl 9‰. Mice were killed at day 3, after echocardiography. Some Balb-C mice received together with ISO antisens oligonucleotides (AOs) directed against QSOX1. In parallel 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.
Results: The ISO Balb-C mice exhibited a decreased shortening fraction (C = 35.0 ± 0.4 %; ISO = 27.2 ± 3.3 %; p<0.001, n=10/group) and increased lung weight/body weight (C=5.2 ± 0.1 mg/g vs. ISO = 6.1±0.2 mg/g, p<0.001). Cardiac QSOX1 (x2, p<0.01) and BNP (x3, p<0.01) transcripts were induced in these mice. QSOX1 silencing by AOs enhanced signs of AHF after ISO (p<0.05 vs. WT+ISO). 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, a BNP (x2 p<0.001) and CD68 (x3, p<0.001) increase were observed only in QSOX1-/-, whereas Galectin 3 increased in both groups.
Conclusion: Using distinct genetic backgrounds and genetic approaches, the data indicated that QSOX1 plays a role in the development of AHF. The absence of QSOX1 leads to a more serious cardiac dysfunction in response to acute cardiac stress by ISO.
Author Disclosures: A. Caillard: None. A. Cescau: None. M. Sadoune: None. M. Meddour: None. Z. Li: None. N. Vodovar: None. A. Mebazaa: None. J. Samuel: None.
- © 2014 by American Heart Association, Inc.