Publications (2)7.08 Total impact
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Article: Role of oxidative stress in cardiac dysfunction of PPARalpha-/- mice.
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ABSTRACT: This study was designed to determine the effects of PPARalpha lack on cardiac mechanical performance and to identify potential intracellular mechanisms linking PPARalpha pathway deficiency to cardiac contractile dysfunction. Echocardiography, ex vivo papillary muscle assays, and in vitro motility assays were used to assess global, intrinsic ventricular muscle performance and myosin mechanical properties, respectively, in PPARalpha(-/-) and age-matched wild-type mice. Three-nitrotyrosine formation and 4-hydroxy-2-nonenal protein-adducts, both markers of oxidative damage, were analyzed by Western blot analysis and immunolabeling. Radical scavenging capacity was analyzed by measuring protein levels and/or activities of the main antioxidant enzymes, including catalase, glutathione peroxidase, and manganese and copper-zinc superoxide dismutases. Echocardiographic left ventricular fractional shortening in PPARalpha(-/-) was 16% lower than that in wild-type. Ex vivo left ventricular papillary muscle exhibited reduced shortening velocity and isometric tension (three- and twofold, respectively). In vitro myosin-based velocity was approximately 20% slower in PPARalpha(-/-), indicating that myosin itself was involved in the contractile dysfunction. Staining of 3-nitrotyrosine was more pronounced in PPARalpha(-/-), and myosin heavy chain was the main nitrated protein. Formation of 3-nitrotyrosine myosin heavy chain was twofold higher in PPARalpha(-/-) and 4-hydroxy-2-nonenal protein-adducts were threefold higher. The expression and activity of manganese superoxide dismutase were respectively 33% and 50% lower in PPARalpha(-/-), with no changes in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase. These findings demonstrate that PPARalpha pathway deficiency impairs cardiac function and also identify oxidative damage to myosin as a link between PPARalpha deficiency and contractile dysfunction.AJP Heart and Circulatory Physiology 08/2007; 293(1):H93-H102. · 3.71 Impact Factor -
Article: Angiographic right and left ventricular function in arrhythmogenic right ventricular dysplasia.
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ABSTRACT: We prospectively documented right ventricular (RV) and left ventricular (LV) volumes and ejection fractions in a large series of patients with arrhythmogenic RV dysplasia/cardiomyopathy (ARVD/C). Eighty-five patients with ARVD/C and 11 controls underwent 2 successive orthogonal right and left monoplane x-ray-digitized cineangiographies. Volumes were calculated using the hemielliptical RV and ellipsoidal LV models. All controls and 58 of 85 patients (ARVD/C-I) had a RV ejection fraction > or =35% and 27 patients had a RV ejection fraction <35% (ARVD/C-II). Tricuspid annulus plane systolic excursion (TAPSE) was lower in ARVD/C-II than in ARVD/C-I patients (6 +/- 3 vs 14 +/- 3 mm) and controls (16 +/- 2 mm) (each p <0.001). In patients with ARVD/C, TAPSE was positively related to RV ejection fraction (r = 0.79) and to crista supraventricularis shortening (r = 0.81) (each p <0.001). Sensitivity and specificity of TAPSE <12 mm in identifying patients with RV ejection fraction <35% were 96% and 78%, respectively. LV ejection fraction was > or =50% in 68 patients, 40% to 49% in 10, and <40% in 7. Diffuse RV outflow tract aneurysm was observed in 9 patients, all belonging to ARVD/C-II, and this sign identified patients with LV ejection fraction <40% with 86% sensitivity and 96% specificity. In conclusion, 68% of ARVD/C patients had normal RV ejection fraction and RV volumes, and 80% of ARVD/C patients had normal LV ejection fraction. Decreased TAPSE <12 mm and a diffuse RV outflow tract aneurysm were sensitive and specific indicators of RV ejection fraction <35% and LV ejection fraction <40%, respectively.The American Journal of Cardiology 04/2004; 93(6):728-33. · 3.37 Impact Factor
