Visualisation of cell death in vivo in patients with acute myocardial infarction

Hofstra, Leo; Liem, Ing Han; Dumont, Ewald A. W. J.; Boersma, Hendrikus H.; Heerde, Waander L. van; Doevendans, Pieter A.; Muinck, Ebo D. de; Wellens, Hein J.J.; Kemerink, Gerrit J.; Reutelingsperger, Chris; Heidendal, G. A. K.

doi:10.1016/s0140-6736(00)02482-x

Cited by 388 publications

(239 citation statements)

References 17 publications

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“…37 Thus, it is reasonable to conceive that if dRib (in vitro) and hypoxia (in vivo) elicit similar pathways of cell death, a different apoptotic susceptibility between Arg þ and Pro þ old individuals in both situations will ensue. In this regard, although the contribution of apoptosis to ischaemic heart is less known than that of necrosis, 43 there is evidence that apoptosis occurs in vivo in ischaemic myocardium, 43 and that both forms of cell death share common mechanisms, especially at the mitochondrial level. 44 At present, the data on our patient's series are not sufficient to disentangle the various causes of the different extents of the ischaemic damages between Arg þ and Pro þ , such as a different extent of the infarct size, a different extension of the atherosclerotic damage, and a different capacity of tissue repairing.…”

Section: Discussionmentioning

confidence: 99%

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death

et al. 2004

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A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg þ ) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro þ ). At variance, the difference in apoptosis susceptibility between Arg þ and Pro þ is not significant when cells from 30-year-old people are studied. Further, we found that Arg þ and Pro þ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg þ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro þ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.

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Section: Discussionmentioning

confidence: 99%

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death

et al. 2004

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“…Activation of HIF-1a reduces reperfusion injury in the heart. [72][73][74] Although HIF-1a has multiple mechanisms to protect the heart, 75 one of the most significant mechanisms particularly relevant for protecting the heart against ischemia/reperfusion could be its effects on cardiac metabolism. 75 Activation of endogenous HIF-1a stimulates the glycolytic pathway 76 and inhibits the TCA cycle 77 and fatty acid oxidation, 78,79 which is beneficial for preserving ATP and reducing O 2 consumption during ischemia/reperfusion.…”

Section: Mechanism Of Autophagy During Ischemiamentioning

confidence: 99%

The role of autophagy in the heart

Kyoi²,

et al. 2008

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Autophagy has evolved as a conserving process that uses bulk degradation and recycling of cytoplasmic components, such as long-lived proteins and organelles. In the heart, autophagy is important for the turnover of organelles at low basal levels under normal conditions and it is upregulated in response to stresses such as ischemia/reperfusion and in cardiovascular diseases such as heart failure. Cardiac remodeling involves increased rates of cardiomyocyte cell death and precedes heart failure. The simultaneously occurring multiple features of failing hearts include not only apoptosis and necrosis but also autophagy as well. However, it has been unclear as to whether autophagy is a sign of failed cardiomyocyte repair or is a suicide pathway for failing cardiomyocytes. The functional role of autophagy during ischemia/reperfusion in the heart is complex. It has also been unclear whether autophagy is protective or detrimental in response to ischemia/reperfusion in the heart. In this review, we will summarize the role of autophagy in the heart under both normal conditions and in response to stress.

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“…15 Recently, Annexin A5 scintigraphy has been developed to detect early signs of cell death in humans in vivo. 16,17 Annexin A5 is an endogenous protein that binds with high affinity to negatively charged phosphatidylserine. 18 Because of an active translocase, phosphatidylserine is located almost exclusively on the inner leaflet of the lipid bilayer of the normal cell membrane.…”

Section: See P 120mentioning

confidence: 99%

Annexin A5 Scintigraphy of Forearm as a Novel In Vivo Model of Skeletal Muscle Preconditioning in Humans

et al. 2005

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Background-Nonlethal ischemia and reperfusion reduce ischemia-reperfusion-induced cell death, a phenomenon called ischemic preconditioning. In animal models, this potent endogenous protection is mimicked in vivo by administration of adenosine. In humans, exploitation of ischemic preconditioning is hindered by the lack of an appropriate in vivo model to study this phenomenon. To solve this problem, we aimed to set up an easy-to-use human in vivo model to study ischemic or pharmacological preconditioning. Methods and Results-Healthy male volunteers performed unilateral ischemic handgrip. At reperfusion, we intravenously injected technetium-99m-labeled Annexin A5, a presumed marker of ischemic injury, and we imaged both forearms and hands simultaneously with a gamma camera. Region of interest analysis (counts per pixel) and subsequent calculation of the percentage difference in radioactivity between experimental and control hands (thenar muscle; meanϮSE) revealed significant uptake to the ischemically exercised tissue (26Ϯ3% at 4 hours after reperfusion; PϽ0.05). This selective localization of Annexin A5 was reduced by ischemic preconditioning (10 minutes of ischemia plus reperfusion before ischemic exercise) or by infusion of adenosine into the brachial artery to 6Ϯ1% and 10Ϯ3%, respectively (PϽ0.05 versus ischemic exercise alone), resembling observations in animal models with infarct size as an end point.Appropriate control experiments supported our conclusion. Conclusions-Annexin

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Visualisation of cell death in vivo in patients with acute myocardial infarction

Cited by 388 publications

References 17 publications

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death

The role of autophagy in the heart

Annexin A5 Scintigraphy of Forearm as a Novel In Vivo Model of Skeletal Muscle Preconditioning in Humans

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