The infarcted myocardium Simply dead tissue, or a lively target for therapeutic interventions

Cleutjens, Jack P.M.; Blankesteijn, W. Matthijs; Daemen, M. J. A. P.; Smits, J. F. M.

doi:10.1016/s0008-6363(99)00212-6

Cited by 234 publications

(216 citation statements)

References 77 publications

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“…If the area at risk remains hypoxic, the myocardium loses its contractile function, becomes necrotic, and fibrotic changes are initiated via the wound-healing process (4,5). Cardiac fibroblasts play an important role in this process.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

2012

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Abstract. When cardiac tissue is exposed to hypoxia, myocytes are damaged, while fibroblasts are activated. However, it is unknown what changes are induced by hypoxia in cardiac fibroblasts. In this study, using the whole cell patch-clamp technique, we investigated the effect of hypoxia on membrane currents in fibroblasts primarily cultured from adult rat hearts. Cardiac fibroblasts were incubated for 24 h under normoxic or hypoxic conditions using Anaeropack. Hypoxia increased a current which reversed at around −20 mV in the cardiac fibroblasts. This current was inhibited by clotrimazole, which is an inhibitor of transient receptor potential melastatin 2 (TRPM2) channel and intermediate-conductance Ca 2+ -activated K + channel (KCa3.1). ADP ribose in the pipette solution enhanced this current. Quantitative RT-PCR revealed that mRNA of TRPM2, but not that of KCa3.1, was increased by hypoxia. RNA interference of TRPM2 prevented the development of the hypoxia-induced current. H 2 O 2 , an activator of TRPM2 channel, induced a higher [Ca 2+ ] i elevation in hypoxia-exposed cardiac fibroblasts than that in normoxia-exposed cells. We conclude that hypoxia induces TRPM2 channel expression in adult rat cardiac fibroblasts.

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Section: Introductionmentioning

confidence: 99%

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

2012

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“…Depending on the degree of success of the therapeutic intervention, the area at risk remains either hypoxic or is fully salvaged. When the area at risk remains hypoxic, the myocardial tissue loses its contractile function and becomes necrotic, leading to the initiation of a wound-healing process (3). This situation is experimentally modeled using the permanent ligation of coronary artery approach (33).…”

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confidence: 99%

Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix

Roy

Khanna

Kuhn

et al. 2006

Physiological Genomics

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Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix. Physiol Genomics 25: 364 -374, 2006. First published March 22, 2006 doi:10.1152/physiolgenomics.00013.2006.-cDNA microarray analysis was performed to screen 15,000 genes and expressed sequence tags (ESTs) to identify changes in the ischemia-reperfused (I-R) rat myocardial transcriptome in the early (day 2) and late (day 7) inflammatory phases of acute myocardial infarction. Lists of candidate genes that were affected by I-R transiently (2 or 7 days only) or on a more sustained basis (2 and 7 days) were derived. The candidate genes represented three major functional categories: extracellular matrix, apoptosis, and inflammation. To expand on the findings from microarray studies that dealt with the two above-mentioned time points, tissues collected from days 0, 0.25, 2, 3, 5, and 7 after reperfusion were examined. Acute myocardial infarction resulted in upregulation of IL-6 and IL-18. Genes encoding extracellular matrix proteins such as types I and III collagen were upregulated in day 2, and that response progressively grew stronger until day 7 after I-R. Comparable response kinetics was exhibited by the candidate genes of the apoptosis category. Caspases-2, -3, and -8 were induced in response to acute infarction. Compared with the myocardial tissue from the sham-operated rats, tissue collected from the infarct region stained heavily positive for the presence of active caspase-3. Laser microdissection and pressure catapulting technology was applied to harvest infarct and adjacent noninfarct control tissue from a microscopically defined region in the rat myocardium. Taken together, this work presents the first evidence gained from the use of DNA microarrays to understand the molecular mechanisms implicated in the early and late inflammatory phases of the I-R heart. heart; oxygen; perceived hyperoxia; wound healing AN ACUTE MYOCARDIAL INFARCTION induces ventricular remodeling, a process that can influence ventricular functions and survival outcomes (22). Ventricular remodeling is directly implicated in postinfarction development of ventricular dilatation, a predictive sign of future congestive heart failure. Timedependent changes in ventricular architecture occur in the infarcted and noninfarcted regions, resulting in hypertrophy of the viable regions of the affected site (6). Cardiac remodeling after myocardial infarction depends on cellular responses, characterized by hypertrophy of myocytes and hyperplasia of interstitial fibroblasts (18). Animals that survive with large transmural infarctions develop heart failure without another ischemic event, as is typically seen in humans. A rat model of myocardial infarction has been extensively studied to understand the functional, structural, and molecular changes associated with clinical ischemic heart disease (23, 33). Substantial alterations in gene expression are needed to afford such profound changes within cells of the remodeling myocar...

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“…0d) group was not quantified in this study. Collagen starts accumulating in infarcted tissue at 2 days after infarction onset [28]. Therefore, Masson's trichrome staining was not suitable for this group since the infarcted hearts were harvested few minutes after coronary ligation.…”

Section: Quantification Of Infarct Size and Thresholdingmentioning

confidence: 99%

Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression

Sirry

Butler

Patnaik

et al. 2016

Journal of the Mechanical Behavior of Biomedical Materials

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Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression, Journal of the Mechanical Behavior of Biomedical Materials, http://dx.doi.org/10.1016Materials, http://dx.doi.org/10. /j.jmbbm.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractUnderstanding the passive mechanical properties of infarcted tissue at different healing stages is essential to explore the emerging biomaterial injection-based therapy for myocardial infarction (MI). Although rats have been widely used as animal models in such investigations, the data in literature that quantify the passive mechanical properties of rat heart infarcts is very limited. MI was induced in rats and hearts were harvested immediately (0 day), 7, 14 and 28 days after infarction onset. Left ventricle anterioapical samples were cut and underwent equibiaxial and non equibiaxial tension followed by uniaxial compression mechanical tests. Histological analysis was conducted to confirm MI and to quantify the size of the induced infarcts. Infarcts maintained anisotropy and the nonlinear biaxial and compressive mechanical behaviour throughout the healing phases with the circumferential direction being stiffer than the longitudinal direction.Mechanical coupling was observed between the two axes in all infarct groups. The 0, 7, 14 and 28 days infarcts showed 438, 693, 1048 and 1218 kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p= 0.0060, 0.0293, and 0.0268 for 0, 7 and 14 days groups). Collagen fibres were found to align in a preferred direction for all infarct groups supporting the observed mechanical anisotropy. The presented data are useful for developing material models for healing infarcts and for setting a baseline for future assessment of emerging mechanical-based MI therapies.

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The infarcted myocardium Simply dead tissue, or a lively target for therapeutic interventions

Cited by 234 publications

References 77 publications

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix

Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression

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