Human Ventricular Myocytesin VitroExhibit both Early and Delayed Preconditioning Responses to Simulated Ischemia

Arstall, Margaret A.; Zhao, Yuansong; Hornberger, Lisa K.; Kennedy, Scott P.; Buchholz, Richard; Osathanondh, R; Kelly, Ralph A.

doi:10.1006/jmcc.1998.0666

Cited by 47 publications

(21 citation statements)

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“…As expected (2,13,28,35,38), subjecting cultured cardiomyocytes to an episode of sublethal hypoxia decreased cell death induced by subsequent simulated lethal ischemiareperfusion, as measured by the MTS and LDH assays (Fig. 1).…”

Section: Resultssupporting

confidence: 75%

“…We also measured the cellular protein levels of HIF-1␣ and the mRNA levels of several HIF-1 target genes in a cultured neonatal rat cardiomyocyte model of preconditioning (2,13,23,28,35,38). Our results suggest that expression of a constitutively stable hybrid HIF-1␣ protects cultured neonatal cardiomyocytes against simulated ischemia-reperfusion injury by inducing multiple protective genes.…”

mentioning

confidence: 86%

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Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Date¹,

Mochizuki²,

Belanger³

et al. 2005

American Journal of Physiology-Cell Physiology

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Section: Resultssupporting

confidence: 75%

mentioning

confidence: 86%

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Date¹,

Mochizuki²,

Belanger³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…This process is relevant not only to coronary artery patients experiencing repetitive ischemia due to coronary artery vasospasm or subocclusions, but also to diabetic patients with microvascular heart disease as well as to hypertensive and cardiomyopathic heart disease patients with increased myocardial wall stress and consequently greater oxygen demand. Ischemic preconditioning has an immediate as well as a delayed component [12,13]. The immediate preconditioning response occurs within minutes to hours [14] and is mediated by ion channels as well as by signaling molecules produced during ischemia [15].…”

Section: Ischemia/reperfusion and Preconditioningmentioning

confidence: 99%

Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia

2007

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Myocardial ischemia, the most common cause of cardiac hypoxia in clinical medicine, occurs when oxygen delivery cannot meet myocardial metabolic requirements in the heart. This deficiency can result from either a reduced supply of oxygen (decreased coronary bloodflow) or an increased myocardial demand for oxygen (increased wall stress or afterload). Patients with stable coronary artery disease as well as patients experiencing acute myocardial infarction can experience episodes of severe ischemia. Although hypoxia is an obligatory component, it is not the sole environmental stress experienced by the ischemic heart. Reperfusion after ischemia is associated with increased oxidative stress as the heart reverts to aerobic respiration and thereby generates toxic levels of reactive oxygen species (ROS). During mild ischemia, mitochondrial function is partially compromised and substrate preferences adapt to sustain adequate ATP generation. With severe ischemia, mitochondrial function is markedly compromised and anaerobic metabolism must provide energy no matter what the cost in generation of toxic ROS adducts. Ischemia produces a variety of environmental stresses that impair cardiovascular function. As a result, multiple signaling pathways are activated in mammalian cells during ischemia/reperfusion injury in an attempt to minimize cellular injury and maintain cardiac output. Amongst the transcriptional regulators activated are members of the hypoxia inducible factor (HIF) transcription factor family. HIF factors regulate a variety of genes that affect a myriad of cellular processes including metabolism, angiogenesis, cell survival, and oxygen delivery, all of which are important in the heart. In this review, we will focus on the metabolic and angiogenic aspects of HIF biology as they relate to the heart during ischemia. We will review the metabolic requirements of the heart under normal as well as hypoxic conditions, the effects of preconditioning and its regulation as it pertains to HIF biology, the apparent roles of HIF-1 and HIF-2 in intermediary metabolism, and translational applications of HIF-1 and HIF-2 biology to cardiac angiogenesis. Increased understanding of the role of HIFs in cardiac ischemia will ultimately influence clinical cardiovascular practice.

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“…Numerous approaches have, to some extent, circumvented this problem. Studies in cells derived from isolated human ventricular myocytes 9,10 and in isolated atrial trabeculae obtained at the time of cardiac surgery 11 suggest that protection can be induced in vitro using metabolic and functional end points, respectively. Moreover, using the same in vitro models, it has been demonstrated that the mechanisms of protection in human tissue closely resemble those observed in many animal species, namely, the involvement of adenosine as an important trigger, protein kinase C as an intermediate intracellular messenger, and the ATP-dependent K ϩ (K ATP ) channel as a potential end-effector protein.…”

Section: Does Preconditioning Occur In the Human Heart?mentioning

confidence: 99%

The Preconditioning Phenomenon

Yellon

Dana

2000

Circulation Research

118

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Abstract-The possibility that an innate mechanism of myocardial protection might be inducible in the human heart has generated considerable excitement and enthusiastic research. The potential to enhance myocardial resistance to ischemic injury in patients suffering the consequences of coronary artery disease has led to studies with more direct clinical relevance. However, in common with many other areas of clinical interest based on advances in basic scientific understanding, early enthusiasm may be disproportionate to ultimate therapeutic significance. There can be little doubt that our understanding of the mechanisms underlying the pathogenesis of ischemia-reperfusion injury has been enhanced significantly by the plethora of research stimulated by interest in endogenous myocardial protection. Direct extrapolation of observations in the laboratory to the cardiology clinic or operating theater is tempting but should be avoided. The results of recent clinical experiments that suggest that preconditioning can protect against ischemia, although encouraging, should be interpreted cautiously, with particular attention to the limitations of the end points available. A reasoned evaluation of recent research should prevent unrealistic expectations and allow improved design of future trials so that this potent adaptive phenomenon can be exploited to its maximum potential. (Circ Res. 2000;87:543-550.)

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Human Ventricular Myocytesin VitroExhibit both Early and Delayed Preconditioning Responses to Simulated Ischemia

Cited by 47 publications

References 0 publications

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia

The Preconditioning Phenomenon

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