scholarly journals Papel del estrés oxidativo y nitrosativo en la hipertrofia cardiaca y remodelación ventricular

2019 ◽  
Vol 35 (2) ◽  
pp. 82-95
Author(s):  
Alejandro Giraldo
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Nitrosative Stress ◽  
Ventricular Remodeling ◽  
Estrés Oxidativo ◽  
Palabras Clave

Objetivo: hacer una revisión de los mecanismos moleculares del estrés oxidativo y nitrosativo en la fisiopatología de la falla cardiaca. Metodología: se hizo una búsqueda en Medline (Pubmed) con las palabras clave: oxidative stress, ventricular remodeling, heart failure y nitrosative stress. Se consultó además bibliografía citada por autores de reconocida trayectoria en investigación en este tema. Resultados: se seleccionaron los 112 artículos más relevantes en el tema de estrés oxidativo/ nitrosativo que se relacionarán con falla cardiaca. Conclusiones: las respuestas de estrés de los cardiomiocitos y del tejido miocárdico es muy probable que constituyan un aspecto significativo del desarrollo de patologías cardiacas que desencadenan como evento final su progresión hacia falla cardiaca. El estrés oxidativo es un tema común en la fisiopatología de la cardiomiopatía isquémica y no isquémica. Patologías cardiacas como la falla cardiaca son usualmente precedidas de hipertrofia cardiaca secundaria, al menos en parte, a la generación de especies reactivas del oxígeno en los cardiomiocitos. Varios son los mecanismos implicados en la remodelación ventricular y progresión de la falla cardiaca que dependen de alteraciones homeostáticas en los sistemas que generan estrés oxidativo y/o nitrosativo. La discusión se centra en la reciente evidencia derivada de investigaciones llevadas a cabo tanto in vitro en cardiomiocitos cultivados como in vivo en modelos experimentales de patologías cardiacas. Las implicaciones clínicas de los recientes descubrimientos aunque son muy prometedoras para la terapéutica de la falla cardiaca, aun no han logrado trasladarse con total éxito a la práctica clínica en los ensayos clínicos realizados hasta el momento

The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Clinical Laboratory ◽  
Left Ventricular ◽  
Control Group ◽  
Reactive Protein ◽  
Lv Mass ◽  
Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

scholarly journals Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction

2009 ◽  
Vol 297 (4) ◽  
pp. C928-C934 ◽  
Author(s):  
Changgong Wu ◽  
Lin Yan ◽  
Christophe Depre ◽  
Sunil K. Dhar ◽  
You-Tang Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cytochrome C ◽  
Protein Expression ◽  
Cell Viability ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Gene

Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF ( P < 0.05 vs. sham), whereas COX II expression remained unchanged. COX III protein expression increased 5-fold after MI and further increased 10-fold after HF compared with sham ( P < 0.05 vs. sham). The physiological impact of COX III regulation was examined in vitro. Overexpression of COX III in mitochondria of HL-1 cells resulted in an 80% decrease in COX I, 60% decrease in global COX activity, 60% decrease in cell viability, and threefold increase in apoptosis ( P < 0.05). Oxidative stress induced by H2O2 significantly ( P < 0.05) increased COX III expression. H2O2 decreased cell viability by 47 ± 3% upon overexpression of COX III, but only by 12 ± 5% in control conditions ( P < 0.05). We conclude that ischemic stress in vivo and oxidative stress in vitro lead to upregulation of COX III, followed by downregulation of COX I expression, impaired COX oxidative activity, and increased apoptosis. Therefore, upregulation of COX III may contribute to the increased susceptibility to apoptosis following MI and subsequent HF.

1, 8-cineole protects against ISO-induced heart failure by inhibiting oxidative stress and ER stress in vitro and in vivo

2021 ◽  
Vol 910 ◽  
pp. 174472
Author(s):  
Yu Wang ◽  
Xuan Zhang ◽  
Yao Fu ◽  
Danni Fu ◽  
Dong Zhen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Er Stress

scholarly journals Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yang Zhao ◽  
Huaxin Sun ◽  
Kai Li ◽  
Luxiang Shang ◽  
Xiaoyan Liang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Fibrosis ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
H9c2 Cells ◽  
Tnf Α ◽  
Underlying Mechanisms

Background. Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. Methods and Results. CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n = 10 ), CHF group (CHF, n = 11 ), Vag group (CHF+vagotomy, n = 10 ), PNU group (CHF+PNU-282987 for 4 weeks, n = 11 ), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n = 10 ). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. Conclusion. CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.

In vivo and in vitro approaches demonstrate proline is not directly involved in the protection against superoxide, nitric oxide, nitrogen dioxide and peroxynitrite

2016 ◽  
Vol 43 (9) ◽  
pp. 870 ◽  
Author(s):  
Santiago Signorelli ◽  
Camila Imparatta ◽  
Marta Rodríguez-Ruiz ◽  
Omar Borsani ◽  
Francisco J. Corpas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitrogen Dioxide ◽  
Time Course ◽  
Nitrosative Stress ◽  
Lotus Japonicus ◽  
Protein Nitration ◽  
Course Content

Plants accumulate proline under diverse types of stresses, and it has been suggested that this α-amino acid has the capacity to protect against oxidative stress. However, it is still controversial whether its protection is due to the direct scavenging of reactive oxygen species (ROS). To solve this issue and considering that nitrosative stress is directly related with an oxidative stress condition, we evaluated whether proline can protect against nitrosative damage. Using proteins of Lotus japonicus (Regel) K.Larsen leaves exposed to a peroxynitrite (ONOO–/ONOOH) generator in presence and absence of 100mM proline, the potential of proline to protect was analysed by the protein nitration profile and NADP-dependent isocitrate dehydrogenase activity, which is inhibited by nitration. In both cases, the presence of proline did not diminish the peroxynitrite effects. Additionally, proline biosynthesis Arabidopsis knockout (KO) mutant plants of Δ(1)-pyrroline-5-carboxylate synthetase1 (P5CS1) gene, designated as Atp5cs1-1 and Atp5cs1-4, showed similar protein nitration levels as wild-type plants under salinity-induced oxidative stress, despite mutants having higher levels of lipid oxidation, H2O2 and superoxide (O2·–). Finally, by a fluorometric assay using specific fluorescent probes, it was determined that the presence of 100mM proline did not affect the time-course content of peroxynitrite or nitric oxide generation in vitro. Our results reveal the relevance of proline accumulation in vivo under stress, but unequivocally demonstrate that proline is not a direct scavenger of peroxynitrite, superoxide, ·NO and nitrogen dioxide (·NO2).

scholarly journals Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction

2020 ◽  
Vol 7 ◽  
Author(s):  
Yan Wang ◽  
Zengshuo Xie ◽  
Nan Jiang ◽  
Zexuan Wu ◽  
Ruicong Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Function ◽  
Specific Inhibitor ◽  
Cardiomyocyte Hypertrophy ◽  
Mitochondrial Morphology ◽  
Protective Effects

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

scholarly journals LCZ696 Ameliorates Oxidative Stress and Pressure Overload-Induced Pathological Cardiac Remodeling by Regulating the Sirt3/MnSOD Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Shi Peng ◽  
Xiao-feng Lu ◽  
Yi-ding Qi ◽  
Jing Li ◽  
Juan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy

Aims. We aimed to investigate whether LCZ696 protects against pathological cardiac hypertrophy by regulating the Sirt3/MnSOD pathway. Methods. In vivo, we established a transverse aortic constriction animal model to establish pressure overload-induced heart failure. Subsequently, the mice were given LCZ696 by oral gavage for 4 weeks. After that, the mice underwent transthoracic echocardiography before they were sacrificed. In vitro, we introduced phenylephrine to prime neonatal rat cardiomyocytes and small-interfering RNA to knock down Sirt3 expression. Results. Pathological hypertrophic stimuli caused cardiac hypertrophy and fibrosis and reduced the expression levels of Sirt3 and MnSOD. LCZ696 alleviated the accumulation of oxidative reactive oxygen species (ROS) and cardiomyocyte apoptosis. Furthermore, Sirt3 deficiency abolished the protective effect of LCZ696 on cardiomyocyte hypertrophy, indicating that LCZ696 induced the upregulation of MnSOD and phosphorylation of AMPK through a Sirt3-dependent pathway. Conclusions. LCZ696 may mitigate myocardium oxidative stress and apoptosis in pressure overload-induced heart failure by regulating the Sirt3/MnSOD pathway.

Abstract 1371: Overexpression Of Mitochondrial Transcription Factor A Protects Failing Myocardium From Oxidative Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masayoshi Yoshida ◽  
Tomomi Ide ◽  
Mayumi Yamato ◽  
Masaki Ikeuchi ◽  
Takaki Tsutsumi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Transcription Factor ◽  
Hela Cells ◽  
Nuclear Dna ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A

Background: Reactive oxygen species (ROS) from mitochondria play a pivotal role in the pathogenesis and progression of heart failure. Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein, in mitochondria promotes transcription of mitochondrial DNA (mtDNA), maintains mtDNA, and increases mtDNA copy number. We previously reported that overexpression of human TFAM ameliorated cardiac remodeling and improved survival by maintaining mitochondrial function. We investigated whether those beneficial effects result from the increase of antioxidative properties both in vivo and in vitro. Methods and Results: [in vivo study] We created myocardial infarction (MI) in wild type (WT) mice and human TFAM transgenic (TG) mice as a model of heart failure. We evaluated free radical generation by in vivo ESR on 28th day after the operation. MI size did not different between WT and MI. Overexpression of TFAM ameliorated MI-induced cardiac hypertrophy (histology) and LV dysfunction (2D echo and cath). Furthermore, the rate of signal decay in in vivo ESR, indicative of oxidative stress, was accelerated in WT-MI (0.10 ± 0.01 vs 0.19 ± 0.02/min, n=4–5, P<0.01) whereas decelerated in TG-MI (0.12 ± 0.02/min; n=4, P<0.01). DNA microarrays analysis of myocardium (8 weeks old, male) indicated that TG overexpressed (double or more) antioxidant relevant genes mostly encoded in nuclear DNA, such as Mthfd2 and Adh1 without affecting mitochondrial respiratory enzyme activities. [in vitro study] We measured superoxide in Hela cells using Dihydroethidium in the presence of rotenone, a complex I inhibitor. Overexpression of TFAM in Hela cells significantly reduced superoxide production (72.8 %). Conclusion: Overexpression of TFAM suppresses ROS. Such an antioxidative property of TFAM may contribute to its powerful anti-remodeling effect in failing heart.

scholarly journals The nuclear receptor RORα protects against angiotensin II-induced cardiac hypertrophy and heart failure

2019 ◽  
Vol 316 (1) ◽  
pp. H186-H200 ◽  
Author(s):  
Ju Youn Beak ◽  
Hong Soon Kang ◽  
Wei Huang ◽  
Page H. Myers ◽  
Dawn E. Bowles ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Myocardial Hypertrophy ◽  
Orphan Receptor ◽  
Ang Ii ◽  
Pathological Hypertrophy

The nuclear receptor retinoic acid-related orphan receptor-α (RORα) regulates numerous critical biological processes, including central nervous system development, lymphocyte differentiation, and lipid metabolism. RORα has been recently identified in the heart, but very little is known about its role in cardiac physiology. We sought to determine whether RORα regulates myocardial hypertrophy and cardiomyocyte survival in the context of angiotensin II (ANG II) stimulation. For in vivo characterization of the function of RORα in the context of pathological cardiac hypertrophy and heart failure, we used the “staggerer” (RORαsg/sg) mouse, which harbors a germline mutation encoding a truncated and globally nonfunctional RORα. RORαsg/sg and wild-type littermate mice were infused with ANG II or vehicle for 14 days. For in vitro experiments, we overexpressed or silenced RORα in neonatal rat ventricular myocytes (NRVMs) and human cardiac fibroblasts exposed to ANG II. RORαsg/sg mice developed exaggerated myocardial hypertrophy and contractile dysfunction after ANG II treatment. In vitro gain- and loss-of-function experiments were consistent with the discovery that RORα inhibits ANG II-induced pathological hypertrophy and cardiomyocyte death in vivo. RORα directly repressed IL-6 transcription. Loss of RORα function led to enhanced IL-6 expression, proinflammatory STAT3 activation (phopho-STAT3 Tyr705), and decreased mitochondrial number and function, oxidative stress, hypertrophy, and death of cardiomyocytes upon ANG II exposure. RORα was less abundant in failing compared with nonfailing human heart tissue. In conclusion, RORα protects against ANG II-mediated pathological hypertrophy and heart failure by suppressing the IL-6-STAT3 pathway and enhancing mitochondrial function. NEW & NOTEWORTHY Mice lacking retinoic acid-related orphan receptor-α (RORα) develop exaggerated cardiac hypertrophy after angiotensin II infusion. Loss of RORα leads to enhanced IL-6 expression and NF-κB nuclear translocation. RORα maintains mitochondrial function and reduces oxidative stress after angiotensin II. The abundance of RORα is reduced in failing mouse and human hearts.

scholarly journals Downregulation of miR-128 Ameliorates Ang II-Induced Cardiac Remodeling via SIRT1/PIK3R1 Multiple Targets

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Heqin Zhan ◽  
Feng Huang ◽  
Qian Niu ◽  
Mingli Jiao ◽  
Xumeng Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Cultured Cells ◽  
Ang Ii ◽  
Stress Injury ◽  
And Oxidative Stress

Recent studies reported that miR-128 was differentially expressed in cardiomyocytes in response to pathologic stress. However, its function and mechanism remain to be fully elucidated. The aim of the present study was to investigate the role of miR-128 in chronic angiotensin II (Ang II) infusion-induced cardiac remodeling and its underlying mechanism. The cardiac remodeling and heart failure in vivo were established in C57BL/6 mice by chronic subcutaneous Ang II delivery. Knocking down miR-128 was conducted in the hearts of the mice by intravenous injection of HBAAV2/9-miR-128-GFP sponge (miR-128 inhibitor). In vitro experiments of cardiac hypertrophy, apoptosis, and aberrant autophagy were performed in cultured cells after Ang II treatment or transfection of miR-128 antagomir. Our results showed that chronic Ang II delivery for 28 days induced cardiac dysfunction, hypertrophy, fibrosis, apoptosis, and oxidative stress in the mice, while the miR-128 expression was notably enhanced in the left ventricle. Silencing miR-128 in the hearts of mice ameliorated Ang II-induced cardiac dysfunction, hypertrophy, fibrosis apoptosis, and oxidative stress injury. Moreover, Ang II induced excessive autophagy in the mouse hearts, which was suppressed by miR-128 knockdown. In cultured cells, Ang II treatment induced a marked elevation in the miR-128 expression. Downregulation of miR-128 in the cells by transfection with miR-128 antagomir attenuated Ang II-induced apoptosis and oxidative injury probably via directly targeting on the SIRT1/p53 pathway. Intriguingly, we found that miR-128 inhibition activated PIK3R1/Akt/mTOR pathway and thereby significantly damped Ang II-stimulated pathological autophagy in cardiomyocytes, which consequently mitigated cell oxidative stress and apoptosis. In conclusion, downregulation of miR-128 ameliorates Ang II-provoked cardiac oxidative stress, hypertrophy, fibrosis, apoptosis, and dysfunction in mice, likely through targeting on PIK3R1/Akt/mTORC1 and/or SIRT1/p53 pathways. These results indicate that miR-128 inhibition might be a potent therapeutic strategy for maladaptive cardiac remodeling and heart failure.

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