Abstract 15123: QSOX1 Function During the Adaptation of the Heart to Angiotensin2 Induced Hypertension
Introduction: Preliminary results from our group suggested a protective role of cardiac QSOX1 induction during acute cardiac stress. QSOX1, a sulfhydryl oxidase, is detected in the media of large arteries and at a lesser extends in the myocardium.
Hypothesis: Using QSOX1-invalidated mice, we analyzed the role of cardiac QSOX1 in response to angiotensin II (AngII)-induced hypertension.
Methods: Adult male QSOX1-/- and WT C57Bl/6 mice (2month-old) were used. Hypertension was induced by infusion of angII (1μg/kg/min) for 28 days using osmotic minipump (Alzet). Cardiovascular parameters were assessed weakly by echocardiography and plethysmography. Expression of natriuretic peptides and genes involved in fibrosis was analyzed by RT-qPCR on cardiac tissue; oxidative stress was detected by using DHE; Fibrosis was analyzed after Sirius red staining.
Results: At baseline, QSOX1-/- mice had a lower blood pressure at baseline (131±2.5 vs. 116±1.6 mmHg, p<0.001), a higher capillary density (Caveolin-Vinculin staining) and a higher arteriolar density (SM actin staining) when compared to WT. In response to AngII, the systolic pressure increased similarly in the two strains (p<0.01 versus normotensive). After 4 weeks of AngII, LV dilatation was aggravated in QSOX1-/-mice (p<0.05) with a decrease in shortening fraction (-12% [-2.9-21], p<0.006), a pulmonary congestion measured by the lung weight to tibia length ratio (p<0.01). Both strains with AngII developed cardiac hypertrophy (heart weight/tibia length (p<0.03); transcription levels of biomarkers of cardiac dysfunction (BNP: p<0.02, ANP: p<0.01, Myh7: P<0.05) were increased in both strains. QSOX1-/- mice with AngII developed more oxidative stress (DHE staining) than AngII WT group associated with more fibrosis (P<0.009) than WT mice (p<0.0001).
Conclusions: The data already obtained suggested that QSOX1 invalidation inhibits some of the cardiac adaptive mechanisms to pressure overload. This data suggest that QSOX1 is involved in the cardiac adaptation to hypertension.
Author Disclosures: A. Caillard: None. M. jérome: None. S. Malha: None. Z. Li: None. A. Mebazaa: None. N. Vodovar: None. J. Samuel: None.
- © 2016 by American Heart Association, Inc.