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  1. AU="Alexander T. Mikhailov"
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  1. Article ; Online: In Search of Novel Targets for Heart Disease

    Alexander T. Mikhailov / Mario Torrado

    Biochemistry Research International, Vol

    Myocardin and Myocardin-Related Transcriptional Cofactors

    2012  Volume 2012

    Keywords Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

    Mario Torrado / Raquel Iglesias / Beatriz Nespereira / Alexander T. Mikhailov

    Journal of Biomedicine and Biotechnology, Vol

    2010  Volume 2010

    Abstract: Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, ... ...

    Abstract Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.
    Keywords Biotechnology ; TP248.13-248.65 ; Chemical technology ; TP1-1185 ; Technology ; T ; DOAJ:Biotechnology ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

    Mario Torrado / Raquel Iglesias / Beatriz Nespereira / Alexander T. Mikhailov

    Journal of Biomedicine and Biotechnology, Vol

    2010  Volume 2010

    Abstract: Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, ... ...

    Abstract Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.
    Keywords Biotechnology ; TP248.13-248.65 ; Medicine ; R
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  4. Article ; Online: Targeted gene-silencing reveals the functional significance of myocardin signaling in the failing heart.

    Mario Torrado / Raquel Iglesias / Alberto Centeno / Eduardo López / Alexander T Mikhailov

    PLoS ONE, Vol 6, Iss 10, p e

    2011  Volume 26392

    Abstract: BACKGROUND: Myocardin (MYOCD), a potent transcriptional coactivator of smooth muscle (SM) and cardiac genes, is upregulated in failing myocardium in animal models and human end-stage heart failure (HF). However, the molecular and functional consequences ... ...

    Abstract BACKGROUND: Myocardin (MYOCD), a potent transcriptional coactivator of smooth muscle (SM) and cardiac genes, is upregulated in failing myocardium in animal models and human end-stage heart failure (HF). However, the molecular and functional consequences of myocd upregulation in HF are still unclear. METHODOLOGY/PRINCIPAL FINDINGS: The goal of the present study was to investigate if targeted inhibition of upregulated expression of myocd could influence failing heart gene expression and function. To this end, we used the doxorubicin (Dox)-induced diastolic HF (DHF) model in neonatal piglets, in which, as we show, not only myocd but also myocd-dependent SM-marker genes are highly activated in failing left ventricular (LV) myocardium. In this model, intra-myocardial delivery of short-hairpin RNAs, designed to target myocd variants expressed in porcine heart, leads on day 2 post-delivery to: (1) a decrease in the activated expression of myocd and myocd-dependent SM-marker genes in failing myocardium to levels seen in healthy control animals, (2) amelioration of impaired diastolic dysfunction, and (3) higher survival rates of DHF piglets. The posterior restoration of elevated myocd expression (on day 7 post-delivery) led to overexpression of myocd-dependent SM-marker genes in failing LV-myocardium that was associated with a return to altered diastolic function. CONCLUSIONS/SIGNIFICANCE: These data provide the first evidence that a moderate inhibition (e.g., normalization) of the activated MYOCD signaling in the diseased heart may be promising from a therapeutic point of view.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Pitx2c is reactivated in the failing myocardium and stimulates myf5 expression in cultured cardiomyocytes.

    Mario Torrado / Diego Franco / Francisco Hernández-Torres / María G Crespo-Leiro / Carmen Iglesias-Gil / Alfonso Castro-Beiras / Alexander T Mikhailov

    PLoS ONE, Vol 9, Iss 3, p e

    2014  Volume 90561

    Abstract: BACKGROUND: Pitx2 (paired-like homeodomain 2 transcription factor) is crucial for heart development, but its role in heart failure (HF) remains uncertain. The present study lays the groundwork implicating Pitx2 signalling in different modalities of HF. ... ...

    Abstract BACKGROUND: Pitx2 (paired-like homeodomain 2 transcription factor) is crucial for heart development, but its role in heart failure (HF) remains uncertain. The present study lays the groundwork implicating Pitx2 signalling in different modalities of HF. METHODOLOGY/PRINCIPAL FINDINGS: A variety of molecular, cell-based, biochemical, and immunochemical assays were used to evaluate: (1) Pitx2c expression in the porcine model of diastolic HF (DHF) and in patients with systolic HF (SHF) due to dilated and ischemic cardiomyopathy, and (2) molecular consequences of Pitx2c expression manipulation in cardiomyocytes in vitro. In pigs, the expression of Pitx2c, physiologically downregulated in the postnatal heart, is significantly re-activated in left ventricular (LV) failing myocardium which, in turn, is associated with increased expression of a restrictive set of Pitx2 target genes. Among these, Myf5 was identified as the top upregulated gene. In vitro, forced expression of Pitx2c in cardiomyocytes, but not in skeletal myoblasts, activates Myf5 in dose-dependent manner. In addition, we demonstrate that the level of Pitx2c is upregulated in the LV-myocardium of SHF patients. CONCLUSIONS/SIGNIFICANCE: The results provide previously unrecognized evidence that Pitx2c is similarly reactivated in postnatal/adult heart at distinct HF phenotypes and suggest that Pitx2c is involved, directly or indirectly, in the regulation of Myf5 expression in cardiomyocytes.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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