Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol

Libera, Luciano Dalla; Ravara, Barbara; Gobbo, Valerio; Danieli-Betto, Daniela; Germinario, Elena; Angelini, Annalisa; Vescovo, Giorgio

doi:10.1016/j.yjmcc.2005.02.023

Cited by 72 publications

(79 citation statements)

References 14 publications

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“…To assess the effect of EUK-134 treatment on oxidative stress, we stained RV tissue slices for nitrotyrosine and analyzed tissue homogenates for protein oxidation using the Oxyblot technique (3,5). The images shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure

Redout

Toorn²,

Zuidwijk

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

110

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have been implicated in the development of pathological ventricular hypertrophy and the ensuing contractile dysfunction. Using the rat monocrotaline (MCT) model of pulmonary arterial hypertension (PAH), we recently reported oxidative stress in the failing right ventricle (RV) with no such stress in the left ventricle of the same hearts. We used the antioxidant EUK-134 to assess the role of ROS in the pathological remodeling and dysfunction of the RV. PAH was induced by an injection of MCT (80 mg/kg, day 0), treatment with EUK-134 (25 mg/kg, once every 2 days) of control and MCT-injected animals [congestive heart failure (CHF) group] was started on day 10, and animals were analyzed on day 22. EUK-134 treatment of the CHF group attenuated cardiomyocyte hypertrophy and associated changes in mRNA expression (myosin heavy chain-␤ and deiodinase type 3). It also reduced RV oxidative stress and proapoptotic signaling and prevented interstitial fibrosis. Cardiac MRI showed that ROS scavenging did not affect the 37% increase in end-diastolic volume of the RV in the CHF relative to the control group, but the threefold increase in end-systolic volume was reduced by 42% in the EUK-134-treated CHF group. The improved systolic function was confirmed using echocardiography by an assessment of tricuspid annular plane systolic excursion. These data indicate an important role of ROS in RV cardiomyocyte hypertrophy and contractile dysfunction due to PAH and show the potential of EUK-class antioxidants as complementary therapeutics in the treatment of RV dysfunction in PAH. right ventricle; fibrosis; monocrotaline PULMONARY ARTERIAL HYPERTENSION (PAH) due to increased pulmonary vascular resistance causes pressure overload of the right ventricle (RV), which, in turn, leads to RV hypertrophy. This response is aimed at normalizing wall stress and may be successfully compensatory, but at higher levels of PAH, pathological remodeling of the RV progresses to dilation and failure (27). RV failure is a principal secondary cause of morbidity and mortality in patients suffering from PAH (20), and the degree of RV remodeling is predictive of patient outcome (38).A previous study (9) in animal models of PAH has suggested a role for ROS in pathological RV remodeling. This was corroborated by a recent study (28) of PAH in rats in which we detected increased oxidative stress in cardiomyocytes of the failing RV. In this study, NADPH oxidase and mitochondria were identified as sources of the increase in ROS production. These changes were specific to the overloaded RV, since they were not observed in the left ventricles (LVs) of the same hearts (28). The oxidative stress may at least in part account for the activation of proapoptotic pathways found in the failing RV in PAH (2) but may also account for other aspects of pathological remodeling. An in vitro study (33) has shown that ROS may act as signaling molecules driving cardiomyocyte hypertrophy. A study (34) of LV remodeling has shown that high cellular ROS levels activate matrix remodeling and i...

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Section: Resultsmentioning

confidence: 99%

“…Bands were visualized by ECL Advanced (Amersham) and quantified using a FujiFilm LAS 3000 laser densitometer. To quantify the level of protein oxidation, we calculated the ratio between densitometric values of the Oxyblot bands and those stained with Ponceau red (3,5).…”

Section: Animalsmentioning

confidence: 99%

Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure

Redout

Toorn²,

Zuidwijk

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

110

View full text Add to dashboard Cite

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“…Bisoprolol and carvedilol therapies have recently been shown to significantly reduce oxidative stress in LV myocardium and skeletal muscle as well as preserve LV function in a DCM rat model. 10,18,23,24) Surprisingly, while the pleiotropic effects of losartan have recently been recognized, 25,26) little is known about the efficiency of losartan when compared with carvedilol in attenuating inflammation and oxidative stress, preserving Cx43 integrity between cardiomyocytes, and suppressing cellular apoptosis in DCM. Therefore, this study tested the hypothesis that losartan therapy is not inferior to carvedilol therapy in improving LV function, upregulating Cx43 protein expression in cardiomyocytes, and down-regulating cardiomyocyte apoptosis by attenuating inflammation, suppressing oxidative stress, and upregulating energy transcription factors in DCM rats.…”

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confidence: 99%

Comparison of Losartan and Carvedilol on Attenuating Inflammatory and Oxidative Response and Preserving Energy Transcription Factors and Left Ventricular Function in Dilated Cardiomyopathy Rats

et al. 2008

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SUMMARYWe compared the effects of losartan and carvedilol on preserving left ventricular (LV) function in an experimental model of dilated cardiomyopathy (DCM) and examined the mechanisms of their pharmacological effects. The rats were divided into group 1 (normal control), group 2 (DCM), group 3 (DCM plus carvedilol 8 mg/kg/day bid orally), and group 4 (DCM plus losartan 20 mg/kg/day orally). All rats were sacrificed on day 90 following DCM induction. The results indicated that connexin43 protein expression and mRNA expressions of peroxisome proliferator-activated receptor-γ coactivator-1α, endothelial nitric oxide synthase, and interleukin-10 were significantly lower, whereas mRNA expressions of endothelin-1 and matrix metalloproteinase-9 were significantly higher in group 2 than in groups 1, 3, and 4 in LV myocardium (all P < 0.05). Additionally, cytochrome C levels in LV myocardium and LV contractility were significantly lower, whereas fibrosis area, cellular apoptosis, and mitochondrial oxidative response of LV myocardium were significantly higher in group 2 than in groups 1, 3, and 4 (all P < 0.005). In conclusion, losartan is comparable to carvedilol in attenuating inflammation, oxidative response, myocardial fibrosis and apoptosis, as well as in preserving energy transcription factors and LV function in DCM. (Int Heart J 2008; 49: 605-619)

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“…[88][89][90] In animal models of CHF, it has been demonstrated that β-blockers protect muscle protein oxidation. 78 Another potential pharmacological strategy is the use of GH and/or IGF-1. In a subgroup of CHF patients with GH deficiency, GH replacement therapy improved clinical status and increased exercise tolerance.…”

Section: Pharmacological Therapiesmentioning

confidence: 99%

Exercise Intolerance in Chronic Heart Failure

Okita

Kinugawa

Tsutsui

2013

Circ J

106

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Chronic heart failure (CHF) is characterized as a clinical disorder displaying exercise intolerance; patients typically complain of early muscular fatigue. Previously, it was thought to be simply a failure of perfusion to the exercising musculature and consequent early onset of intramuscular acidosis in CHF. However, improved hemodynamics by cardiotonic agents did not lead to an increase in exercise tolerance. Later studies have shown that intrinsic skeletal muscle abnormalities exist in patients with CHF and could induce the early anaerobic metabolism that limits exercise tolerance. We review the clinical importance of skeletal muscle abnormalities in patients with CHF. Considering the significance of peripheral muscle abnormalities and their development might help physicians and researchers better understand the mechanisms of well-established exercise training and pharmacological therapies that have been shown to improve the prognosis for CHF, and thus develop potential novel therapies. (Circ J 2013; 77: 293 -300)

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Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol

Cited by 72 publications

References 14 publications

Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure

Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure

Comparison of Losartan and Carvedilol on Attenuating Inflammatory and Oxidative Response and Preserving Energy Transcription Factors and Left Ventricular Function in Dilated Cardiomyopathy Rats

Exercise Intolerance in Chronic Heart Failure

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