Antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction

Oskarsson, Helgi; Coppey, Lawrence J.; Weiß, Robert M.; Li, Wei-Gen

doi:10.1016/s0008-6363(99)00400-9

Cited by 83 publications

(38 citation statements)

References 46 publications

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“…In fact, recent studies have suggested cardiac myocyte apoptosis contributes to LV remodeling after MI. 26,27 Importantly, increased oxidative stress occurs concomitantly with increased cardiac myocyte apoptosis within the noninfarcted area. This is a provoking observation, because oxidative stress is a powerful inducer of apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Ide²,

et al. 2006

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Background-Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. Methods and Results-We created MI in 12-to 16-week-old, male Prx-3-transgenic mice (TGϩMI, nϭ37) and nontransgenic wild-type mice (WTϩMI, nϭ39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TGϩMI than in WTϩMI mice (meanϮSEM, 1.5Ϯ0.2 vs 2.2Ϯ0.2 nmol/mg protein; nϭ8 each, PϽ0.05). LV cavity dilatation and dysfunction were attenuated in TGϩMI compared with WTϩMI mice, with no significant differences in infarct size (56Ϯ1% vs 55Ϯ1%; nϭ6 each, PϭNS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TGϩMI mice were also larger than those in WTϩsham-operated mice but smaller than those in WTϩMI mice. Improvement in LV function in TGϩMI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WTϩMI mice, and this decrease was also ameliorated in TGϩMI mice. Conclusions-Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Ide²,

et al. 2006

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“…Larger myocardial infarction results in escalated reoxygenation, what is probably associated with incomplete normalization of ST-segment depression. 15 Significant reoxygenation injury is related to increased apoptosis in the remote part of the myocardium, which can affect mortality, 15 and can be considered as another explanation for the observed correlation between the lack of STN and long-term mortality. However, it is only hypothesis and should be confirmed in the future studies.…”

Section: Discussionmentioning

confidence: 99%

Lack of ST-Segment Depression Normalization After PCI is a Predictor of 5-Year Mortality in Patients With ST-Elevation Myocardial Infarction

Kożuch

Dobrzycki

Nowak

et al. 2007

Circ J

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T-segment changes reflect ischemic disturbances in the myocardium and the significance of ST-segment changes during acute coronary syndrome (ACS) has been confirmed by the fact that the spectrum of patients is divided according to ST-segment changes, with consequences in subsequent treatment strategies.The significance of dynamic changes in the elevated STsegment in patients with ST-elevation myocardial infarction (STEMI) has been described and assessment of an early resolution of ST-segment elevation has become an established method-predicting outcome. 1 ST-segment depression in patients with non-ST elevation ACS is a consequence of ischemia and is commonly used for risk stratification of such patients. ST-segment depression can also appear in patients with STEMI. The phenomenon of ST-segment depression in the leads opposite to the elevation-leads in patients with STEMI was extensively studied in the 80 s and was mostly observed in patients with STEMI. Reports on the relevance of changes in the ST-segment remote from the zone of an acute infarct have reached disparate conclusions, 2,3 so it has been considered not only as a reciprocal electrical change (mirror image) but also a Circulation Journal Vol.71, December 2007 reaction to local ischemia. On the one hand, reciprocal STsegment depression on the presenting ECG has been described as a benign electrical phenomenon related to the time from the start of symptoms, which does not predict adverse events. 2 On the other hand, reciprocal ST depression was found to be a response to ischemia in territory distant from the site of infarction, and was associated with a higher risk of fatal arrhythmias and late morbidity. 3 Furthermore, inferior ST-segment depression during an anterior infarction was shown to be associated with more extensive infarction, greater morbidity and higher frequency of multivessel coronary disease, which suggested that ST depression was not a reciprocal change, but rather ischemia in adjacent remote regions. 4 However, the significance of the dynamic changes in the reciprocal ST-segment depression after interventional treatment of patients with STEMI is unknown and became the aim of this study. Methods Study PopulationThe Lack of ST-Segment Depression Normalization After PCI is a Predictor of 5-Year Mortality in Patients With ST-Elevation Myocardial InfarctionMarcin Kozuch, MD; Slawomir Dobrzycki, MD, PhD; Konrad Nowak, MD; Przemyslaw Prokopczuk, MD, PhD; Pawel Kralisz, MD; Hanna Bachorzewska-Gajewska, MD, PhD; Karol Kaminski, MD, PhD*; Anna Kozieradzka, MD*; Janusz Korecki, MD, PhD; Boguslaw Poniatowski, MD, PhD; Wlodzimierz Jerzy Musial, MD, PhD* Background The significance of dynamic changes in a depressed ST-segment in the reciprocal changes after percutaneous coronary intervention (PCI) of patients with ST-elevation myocardial infarction (STEMI) is unknown, so the aim of this study was to evaluate the significance of reciprocal ST-segment depression normalization (STN) on long-term mortality in patients with STEMI treated with primary...

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“…Decreased infarct size in superoxide dismutase (SOD)-producing transgenic mice suggests direct evidence for the role of involvement of ROS in MI. 22,23 In limited investigations, the use of antioxidants such as mercaptopropionyl glycine, edaravone and probucol have demonstrated varied effects on remodeling in animal models of MI, [24][25][26][27][28][29][30][31][32] with improvement in collagen content and histological changes. In this study, we sought to delineate the role of chronic tobacco smoke leading up to an acute MI by focusing on oxidative stress coupled with inflammation in the genesis of events leading to cardiac dysfunction and histological extent of damage.…”

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confidence: 99%

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Khanna

Mehra

2012

Laboratory Investigation

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The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92 ± 0.41 vs 3.45 ± 0.33; Po0.05), and tobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; Po0.01) rats. Decreased intracardiac mRNA expression of the markers of inflammation, tissue repair and oxidative stress and circulating levels of pro-inflammatory cytokines accompanied these positive effects of NAC. The treatment of tobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7 ± 0.12 vs 10 ± 0.18; Pp0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking. Globally, tobacco smoke exposure remains a significant risk for the development of acute myocardial infarction (MI) irrespective of ethic or gender disparities. Exposure to tobacco smoke increases inflammation, oxidative stress 1-10 and decreases antioxidant expression. [11][12][13][14][15] Direct and indirect studies have demonstrated that oxidative stress from reactive oxygen species (ROS) generated through mitochondria, xanthine oxidase, and the NADPH oxidase system 16-21 is one of the important factors in the pathogenesis of myocardial ischemia. Decreased infarct size in superoxide dismutase (SOD)-producing transgenic mice suggests direct evidence for the role of involvement of ROS in MI. 22,23 In limited investigations, the use of antioxidants such as mercaptopropionyl glycine, edaravone and probucol have demonstrated varied effects on remodeling in animal models of MI, [24][25][26][27][28][29][30][31][32] with improvement in collagen content and histological changes. In this study, we sought to delineate the role of chronic tobacco smoke leading up to an acute MI by focusing on oxidative stress coupled with inflammat...

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Antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction

Abstract: Long-term treatment with the antioxidants probucol and pyrrolidine dithiocarbamate attenuates oxidative stress, myocyte apoptosis, caspase-3 like activity and the expression of p53, bax and caspase-3 within RM in rats after a large myocardial infarction.

Cited by 83 publications

References 46 publications

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Lack of ST-Segment Depression Normalization After PCI is a Predictor of 5-Year Mortality in Patients With ST-Elevation Myocardial Infarction

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

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