Oxidative stress in congestive heart failure

Singal, Pawan K.; Khaper, Neelam; Farahmand, Firoozeh; Belló‐Klein, Adriane

doi:10.1007/s11886-000-0070-x

Cited by 53 publications

(37 citation statements)

References 62 publications

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“…Combined with previous extensive in vitro studies on the inhibitory role of Cav-1͞caveolae on eNOS activity, our study suggests that Cav-1 inhibition of eNOS may be critical in preventing the dysregulation of systemic NO levels. Because high NO levels have been reported in cardiomyopathy and pulmonary hypertension in both human and animal models (44,(50)(51)(52)(53)(54)(55)(56)(57), it is likely that chronic and dramatic elevations in systemic NO levels caused by the loss of Cav-1 and caveolae may contribute the cardiopulmonary defects. It will become of interest to see whether defects in the cav-1 gene are represented in patient populations with idiopathic dilated cardiomyopathy.…”

Section: Cav-1 Deficiency Causes Pulmonary Hypertension and Resultingmentioning

confidence: 99%

Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice

Zhao

Liu

Stan

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

432

382

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Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the in vivo significance of Caveolins in mammals, we generated mice deficient in the caveolin-1 (cav-1) gene and have shown that, in the absence of Cav-1, no caveolae structures were observed in several nonmuscle cell types. Although cav-1 ؊/؊ mice are viable, histological examination and echocardiography identified a spectrum of characteristics of dilated cardiomyopathy in the left ventricular chamber of the cav-1-deficient hearts, including an enlarged ventricular chamber diameter, thin posterior wall, and decreased contractility. These animals also have marked right ventricular hypertrophy, suggesting a chronic increase in pulmonary artery pressure. Direct measurement of pulmonary artery pressure and histological analysis revealed that the cav-1 ؊/؊ mice exhibit pulmonary hypertension, which may contribute to the right ventricle hypertrophy. In addition, the loss of Cav-1 leads to a dramatic increase in systemic NO levels. Our studies provided in vivo evidence that cav-1 is essential for the control of systemic NO levels and normal cardiopulmonary function.

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Section: Cav-1 Deficiency Causes Pulmonary Hypertension and Resultingmentioning

confidence: 99%

Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice

Zhao

Liu

Stan

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

432

382

View full text Add to dashboard Cite

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“…Evidence has accumulated that oxidative stress is increased in experimental and human heart failure (43) and that increased oxidative stress may contribute to the progression of heart failure (24). Recent studies have shown that carvedilol acting Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, carvedilol exhibits ␣-adrenergic blocking and potent antioxidant properties (51). This antioxidant effect of carvedilol may be clinically important because oxygen free radicals, which have been shown to increase in heart failure (43), can cause myocyte apoptosis (4), myocardial ␤-adrenergic receptor signal transduction abnormalities (21), and contractile dysfunction (6). In a recent study (35), we report that left ventricular mechanical function improved with antioxidant vitamins in animals with tachypacing-induced cardiomyopathy.…”

mentioning

confidence: 99%

Importance of antioxidant and antiapoptotic effects of β-receptor blockers in heart failure therapy

Kawai

Qin

Shite

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Importance of antioxidant and antiapoptotic effects of ␤-receptor blockers in heart failure therapy. Am J Physiol Heart Circ Physiol 287: H1003-H1012, 2004. First published April 22, 2004 10.1152/ajpheart.00797.2003.-The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its ␤-adrenergic blocking, antioxidant, and/or ␣-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2Ј-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension (r ϭ Ϫ0.678, P Ͻ 0.0001), fractional shortening (r ϭ 0.706, P Ͻ 0.0001), and apoptotic myocytes (r ϭ Ϫ0.473, P ϭ 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of ␤-receptors in the treatment of CHF.carvedilol; metoprolol; oxidative stress; myocytes apoptosis; myocyte hypertrophy.RECENT STUDIES HAVE SHOWN that ␤-adrenergic receptor blockers such as carvedilol, metoprolol, and bisoprolol are efficacious in the treatment of congestive heart failure (CHF) (3). These agents not only increase left ventricular systolic function (15, 28, 30) but also reduce cardiac mortality and morbidity in patients with CHF (7,23,(31)(32)(33). However, the extent of improvements produced by these agents varies, with the greatest improvement in mortality with carvedilol (31). In a direct comparison study published recently (33), carvedilol was shown to produce a greater survival benefit in patients with CHF than metoprolol. Whereas the discrepancies among the studies may relate to the difference in patient populations or degree of ␤-receptor blockade, these ␤-adrenergic blockers may have additional properties that contribute to their different clinical benefits. Unlike metoprolol and bisoprolol, which are sel...

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“…Recently, increases in plasma biochemical markers of oxidative stress have been reported in patients with HF (17,18). There is a definitive correlation between oxidative stress and ventricular dysfunction (2,4).…”

Section: Discussionmentioning

confidence: 99%