Heart failure with preserved ejection fraction: Defining the function of ROS and NO

Zuo, Li; Chuang, Chia Chen; Hemmelgarn, Benjamin T.; Best, Thomas M.

doi:10.1152/japplphysiol.01149.2014

Cited by 37 publications

(28 citation statements)

References 71 publications

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“…Further study found that H 2 O 2 -induced ROS production could largely be reversed by RHL. Oxidative stress is also suggested to activate cell apoptosis, thereby enhancing CHF especially in the advanced stages (20,21). Then, TUNEL staining was carried out and the results showed that H 2 O 2 markedly primary cardiomyocytes apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

et al. 2018

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Abstract. The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal rat ventricular myocytes (NRVMs) and congestive heart failure induced by co-arctation of the abdominal aorta. Male Sprague-Dawley rats were divided into 3 groups randomly: co-arctation of abdominal aorta group (A group, n=10), sham operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To establish an in vitro oxidative stressed cardiomyocyte model, NRVMs were treated with 10 µM H 2 O 2 for 24 h. MTT assay indicated that H 2 O 2 treatment reduced primary cardiomyocyte viability in a time-and dose-dependent manner, whereas RHL abolished the detrimental effects of H 2 O 2 , indicating a protective role of RHL. Further study demonstrated that H 2 O 2 -induced reactive oxygen species (ROS) production was reversed by RHL. Then, TUNEL staining was carried out and the results revealed that H 2 O 2 markedly enhanced primary cardiomyocyte apoptosis. Conversely, RHL incubation decreased H 2 O 2 -induced cell apoptosis, indicating the protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38 activation was identified in the failed heart. Notably, treatment with RHL reduced p38 activation. In addition, RHL significantly enhanced the expression of anti-apoptotic protein, B cell lymphoma (Bcl)-2, however markedly reduced the protein level of Bcl-2 associated X, apoptosis regulator in primary cardiomyocytes, indicating its anti-apoptotic role in the cardiac setting. Overall, RHL protects heart failure primarily by reducing ROS production and cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase activation.

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Section: Discussionmentioning

confidence: 99%

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

et al. 2018

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“…Reactive oxygen species are involved in many diseases, including neurological diseases (Zuo et al, 2015b), heart failure (Zuo et al, 2015a) and hypertension (Zuo et al, 2014b). A large number of studies have shown that ischemic postconditioning can significantly reduce ROS production, thereby reducing myocardial I/R injury (Barsukevich et al, 2015; Singh et al, 2012; Zhao et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

Xie

et al. 2017

PeerJ

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BackgroundSevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2–STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2–STAT3 signal pathway.MethodsAn adult male Sprague–Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus. At the beginning of reperfusion, 2.4% sevoflurane alone or in combination with AG490 (a JAK2 selective inhibitor) was used as a postconditioning treatment. The cardiac function indicators, myocardial infarct size, lactic dehydrogenase (LDH) release, mitochondrial ultrastructure, mitochondrial reactive oxygen species (ROS) generation rates, ATP content, protein expression of p-JAK, p-STAT3, Bcl-2 and Bax were measured.ResultsCompared with the I/R group, S-post significantly increased the expression of p-JAK, p-STAT3 and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the myocardial infarction areas, improved the cardiac function indicators and the mitochondrial ultrastructure, decreased the mitochondrial ROS and increased the ATP content. However, the cardioprotective effects of S-post were abolished by treatment with a JAK2 selective inhibitor (p < 0.05).ConclusionThis study demonstrates that the cardioprotective effects of S-post are associated with the activation of JAK2–STAT3. The mechanism may be related to an increased expression of p-JAK2 and p-STAT3 after S-post, which reduced mitochondrial ROS generation and increased mitochondrial ATP content, thereby reducing apoptosis and myocardial infarct size.

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“…In HF patients, increased UA production occurs owing to the hypoxia on the microvasculature and impaired oxidative metabolism with increased amount and activity of XO in capillary endothelial cells (2). Increased oxidative stress induces impaired contractile function, endothelial dysfunction, and skeletal muscle impairment, thereby contributing to disease progression in HF (31,35). Accordingly, several studies have elucidated the beneficial effects of UA-lowering therapy with the XO inhibitor allopurinol for physiological endpoints such as endothelial dysfunction (10), peripheral blood flow (9), and energetic inefficiency of myocardium (6).…”

Section: Discussionmentioning

confidence: 99%

“…Heart failure with preserved ejection fraction (HFpEF), which constitutes approximately half of all HF patients, has a poor prognosis similar to heart failure with reduced ejection fraction (HFrEF), but the pathogenesis of HFpEF has not yet been clearly defined (16). HFpEF patients tend to have multiple noncardiac comorbidities, and several pathophysiological factors contribute to the pathogenesis of HFpEF (15,17,35), which substantially differs from that of HFrEF (4,26). Several biomarkers have been identified to estimate the prognosis and select the appropriate therapy for chronic HF patients (34).…”

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confidence: 99%

Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction

Shimizu

Yoshihisa

Kanno

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group (n = 170), the hyperuricemia group (n = 254) had a higher prevalence of hypertension (P = 0.013), diabetes mellitus (P = 0.01), dyslipidemia (P = 0.038), atrial fibrillation (P = 0.001), and use of diuretics (P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and V̇e/V̇co2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V̇o2 (14.9 vs. 17.9 ml·kg(-1)·min(-1), P < 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia (P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036-3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

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Heart failure with preserved ejection fraction: Defining the function of ROS and NO

Cited by 37 publications

References 71 publications

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction

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