Diagnosis of sudden cardiac death due to early myocardial ischemia: An ultrastructural and immunohistochemical study

Visonà, Silvia Damiana; Benati, Donatella; Monti, Maria Cristina; Galiè, Mirco; Andrello, L.; Frontini, Andrea; Osculati, Antonio Marco Maria

doi:10.4081/ejh.2018.2866

Cited by 18 publications

(16 citation statements)

References 31 publications

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“…Formalin-Fixed Paraffin-Embedded (FFPE) LV tissue from a CMP patient with a LARGE1 promoter variant and controls without LARGE1 variants were used for IHC analysis using standard techniques 116 . FFPE tissue blocks were sectioned at 4 μ m, dewaxed in xylene, dehydrated with a serial dilution of ethanol solution and washed with PBS.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy

Lesurf

Said

Akinrinade

et al. 2020

Preprint

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Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20 to 30 percent of cases. The contribution of variants in noncoding DNA elements that regulate gene expression has not been explored. We performed whole genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein coding variants in known CMP genes, 5% cases harbored rare loss of function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high risk variants in promoters and enhancers of CMP genes in an additional 20 percent cases (Odds ratio 2.14, 95 percent CI 1.60-2.86, p equals 5.26E-07 vs 1326 controls) with genes involved in alpha-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) specifically enriched for regulatory variants (False discovery rate less than 0.03). These findings were independently replicated in the Genomics England CMP cohort (n=1266). The functional effect of non-coding variants on transcription was functionally validated in patient myocardium and reporter assays in human cardiomyocytes, and that of novel gene variants in zebrafish knockouts. Our results show that functionally active variants in novel genes and in regulatory elements of CMP genes contribute strongly to the genomic etiology of childhood-onset CMP.

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Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy

Lesurf

Said

Akinrinade

et al. 2020

Preprint

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“…Various studies have shown that remodeling of connexin expression and gap junction organization occurs in adult heart conditions such as arrhythmia, ischemic heart disease, and sudden cardiac death ( Severs et al, 2008 ; Molina et al, 2018 ; Visoná et al, 2018 ). Alterations can occur in the distribution, amount, and type of connexin expression during different types of heart disease in humans.…”

Section: Absorptionmentioning

confidence: 99%

Overview of the Components of Cardiac Metabolism

Hausner

Elmore

Yang

2019

Drug Metabolism and Disposition

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Metabolism in organs other than the liver and kidneys may play a significant role in how a specific organ responds to chemicals. The heart has metabolic capability for energy production and homeostasis. This homeostatic machinery can also process xenobiotics. Cardiac metabolism includes the expression of numerous organic anion transporters, organic cation transporters, organic carnitine (zwitterion) transporters, and ATP-binding cassette transporters. Expression and distribution of the transporters within the heart may vary, depending on the patient's age, disease, endocrine status, and various other factors. Several cytochrome P450 (P450) enzyme classes have been identified within the heart. The P450 hydroxylases and epoxygenases within the heart produce hydroxyeicosatetraneoic acids and epoxyeicosatrienoic acids, metabolites of arachidonic acid, which are critical in regulating homeostatic processes of the heart. The susceptibility of the cardiac P450 system to induction and inhibition from exogenous materials is an area of expanding knowledge, as are the metabolic processes of glucuronidation and sulfation in the heart. The susceptibility of various transcription factors and signaling pathways of the heart to disruption by xenobiotics is not fully characterized but is an area with implications for disruption of normal postnatal development, as well as modulation of adult cardiac health. There are knowledge gaps in the timelines of physiologic maturation and deterioration of cardiac metabolism. Cross-species characterization of cardiac-specific metabolism is needed for nonclinical work of optimum translational value to predict possible adverse effects, identify sensitive developmental windows for the design and conduct of informative nonclinical and clinical studies, and explore the possibilities of organ-specific therapeutics.

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“…The ultrastructural morphological approach at TEM has been widely used in basic and applied biomedical research for the study of different tissues under unperturbed or experimental conditions: tooth structure and repair; 47 , 48 white adipose tissue classification; 49 , 50 stem cells culture for reconstructive purpose; 51 , 52 skeletal muscle features under experimental 53 , 54 and pathological 55 , 56 conditions; liver response to pretransplantation treatment; 57 female reproductive organs 58 and explanted oocytes for in vitro reproduction; 59 , 60 post-implant skin modification; 61 autopsy myocardium for diagnostic purposes 62 .…”

Section: May Electron Microscopy Still Make a Relevant Contribution Tmentioning

confidence: 99%

Ultrastructural histochemistry in biomedical research: Alive and kicking

Malatesta

2018

Eur J Histochem

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The high-resolution images provided by the electron microscopy has constituted a limitless source of information in any research field of life and materials science since the early Thirties of the last century. Browsing the scientific literature, electron microscopy was especially popular from the 1970’s to 80’s, whereas during the 90’s, with the advent of innovative molecular techniques, electron microscopy seemed to be downgraded to a subordinate role, as a merely descriptive technique. Ultra -structural histochemistry was crucial to promote the Renaissance of electron microscopy, when it became evident that a precise localization of molecules in the biological environment was necessary to fully understand their functional role. Nowadays, electron microscopy is still irreplaceable for ultrastructural morphology in basic and applied biomedical research, while the application of correlative light and electron microscopy and of refined ultrastructural histochemical techniques gives electron microscopy a central role in functional cell and tissue biology, as a really unique tool for high-resolution molecular biology in situ.

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Diagnosis of sudden cardiac death due to early myocardial ischemia: An ultrastructural and immunohistochemical study

Cited by 18 publications

References 31 publications

Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy

Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy

Overview of the Components of Cardiac Metabolism

Ultrastructural histochemistry in biomedical research: Alive and kicking

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