Metabolic derangement in ischemic heart disease and its therapeutic control

Ferrari, Roberto; Pepi, Patrizia; Ferrari, Federica; Nesta, Francesca; Benigno, Massimo; Visioli, O

doi:10.1016/s0002-9149(98)00531-1

Cited by 43 publications

(33 citation statements)

References 54 publications

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“…So far, therapeutic attempts to prevent reperfusion injury are limited to relatively smallscale studies testing the administration of vitamin E (24), calcium antagonists (25), early use of ACE inhibitors, sulfhydrylrich reagents such as N-acetylcysteine, magnesium, and various free radical scavengers (26). However, accelerated myocyte necrosis and destruction related to reoxygenation of the ischemic myocardium continues to represent a clinically relevant question.…”

Section: Discussionmentioning

confidence: 99%

Activation of Poly(ADP-Ribose) Polymerase by Myocardial Ischemia and Coronary Reperfusion in Human Circulating Leukocytes

Tóth-Zsámboki

Horváth

Vargová

et al. 2006

Mol Med

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Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI.

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Section: Discussionmentioning

confidence: 99%

Activation of Poly(ADP-Ribose) Polymerase by Myocardial Ischemia and Coronary Reperfusion in Human Circulating Leukocytes

Tóth-Zsámboki

Horváth

Vargová

et al. 2006

Mol Med

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“…Mitochondrial dysfunction in ischemia-reperfusion injury is caused by oxidative stress (1)(2)(3)(4)(5)(6). In the post-ischemic heart, oxygen delivery to the myocardium is not sufficient to meet the need for mitochondrial oxidation during the physiological conditions of hypoxia, leaving the mitochondrial electron transport chain (ETC) 2 in a more reduced state.…”

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confidence: 99%

Mitochondrial Complex II in the Post-ischemic Heart

Chen

Chen²,

Pfeiffer

et al. 2007

Journal of Biological Chemistry

215

111

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“…Multiple factors are likely to have a role in the protective effect of ACE inhibitors in ischemia-reperfusion injury: they decrease leukocyte infiltration 28 , possess anti-inflammatory effects 29 and free radical scavenging properties 30 , and effect mediated by increase the levels of bradykinin and prostaglandin 31 . Because ACE inhibition can increase circulating levels of angiotensin-(1-7) 32 , this may mediate some of these cardiovascular effects 33,34 .…”

Section: Discussionmentioning

confidence: 99%