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Animal Models and "Omics" Technologies for Identification of Novel Biomarkers and Drug Targets to Prevent Heart Failure.

Hou Y, Adrian-Segarra JM, Richter M, Kubin N, Shin J, Werner I, Walther T, Schönburg M, Pöling J, Warnecke H, Braun T, Kostin S, Kubin T - Biomed Res Int (2015)

Bottom Line: Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate.To achieve this, various animal models in combination with an "omics" toolbox can be used.These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.

ABSTRACT
It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an "omics" toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.

No MeSH data available.


Related in: MedlinePlus

Cardiomyocytes respond to stress by membranous translocation of ERM proteins. (a) Fluorescence micrographs of freshly isolated adult rat cardiomyocytes (4 hours) show different degrees of ezrin translocation (yellow arrows). Ezrin is usually located at the intercalated disc (white arrows) but upon translocation it is detected laterally of the membrane. (b) Fluorescence micrographs demonstrate massive translocation of ezrin. Ezrin is part of the cell blebs which are, when occurring to this extent, characteristic for dying cells. (c) Fluorescence micrographs show increases and accumulation of ezrin in cell extensions of IGF-1 stimulated adult cardiomyocytes after seven days. Note that serum shows also some effects on ezrin localization in control cultures (Con). (d) Fluorescence images of oncostatin M receptor-β siRNA treated adult rat cardiomyocytes (OSM + siOβ) in culture demonstrate successful interruption of OSM induced remodeling after 7 days. Con indicates albumin treated control cultures.
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fig3: Cardiomyocytes respond to stress by membranous translocation of ERM proteins. (a) Fluorescence micrographs of freshly isolated adult rat cardiomyocytes (4 hours) show different degrees of ezrin translocation (yellow arrows). Ezrin is usually located at the intercalated disc (white arrows) but upon translocation it is detected laterally of the membrane. (b) Fluorescence micrographs demonstrate massive translocation of ezrin. Ezrin is part of the cell blebs which are, when occurring to this extent, characteristic for dying cells. (c) Fluorescence micrographs show increases and accumulation of ezrin in cell extensions of IGF-1 stimulated adult cardiomyocytes after seven days. Note that serum shows also some effects on ezrin localization in control cultures (Con). (d) Fluorescence images of oncostatin M receptor-β siRNA treated adult rat cardiomyocytes (OSM + siOβ) in culture demonstrate successful interruption of OSM induced remodeling after 7 days. Con indicates albumin treated control cultures.

Mentions: In order to accelerate the discovery of disease-relevant peptides animal culture models provide “simplified” systems for the analysis on an “omics” platform (Figure 3(a)). Primary cultures of cardiomyocytes are particularly suitable for “omics” studies, since adult cardiomyocytes are terminally differentiated and they transfer their epigenetic, genomic, and proteomic in vivo status into the culture dish, which might not be preserved in cell lines or passaged cells [37]. Primary cultures are, as defined by the Latin term “primus,” cells which are directly used for experiments after isolation from the animal and not further passaged. The strong correlation we demonstrated between differentially regulated proteins of remodeling cardiomyocytes in vivo and in vitro [6, 14, 15] has permitted us to find ERM proteins (Figures 3 and 4) and other potentially relevant candidates [6, 15, 31] in oncostatin M (Figure 2(b)) and IGF-1 (insulin-like growth factor-1) stimulated cultures of adult rat cardiomyocytes.


Animal Models and "Omics" Technologies for Identification of Novel Biomarkers and Drug Targets to Prevent Heart Failure.

Hou Y, Adrian-Segarra JM, Richter M, Kubin N, Shin J, Werner I, Walther T, Schönburg M, Pöling J, Warnecke H, Braun T, Kostin S, Kubin T - Biomed Res Int (2015)

Cardiomyocytes respond to stress by membranous translocation of ERM proteins. (a) Fluorescence micrographs of freshly isolated adult rat cardiomyocytes (4 hours) show different degrees of ezrin translocation (yellow arrows). Ezrin is usually located at the intercalated disc (white arrows) but upon translocation it is detected laterally of the membrane. (b) Fluorescence micrographs demonstrate massive translocation of ezrin. Ezrin is part of the cell blebs which are, when occurring to this extent, characteristic for dying cells. (c) Fluorescence micrographs show increases and accumulation of ezrin in cell extensions of IGF-1 stimulated adult cardiomyocytes after seven days. Note that serum shows also some effects on ezrin localization in control cultures (Con). (d) Fluorescence images of oncostatin M receptor-β siRNA treated adult rat cardiomyocytes (OSM + siOβ) in culture demonstrate successful interruption of OSM induced remodeling after 7 days. Con indicates albumin treated control cultures.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508378&req=5

fig3: Cardiomyocytes respond to stress by membranous translocation of ERM proteins. (a) Fluorescence micrographs of freshly isolated adult rat cardiomyocytes (4 hours) show different degrees of ezrin translocation (yellow arrows). Ezrin is usually located at the intercalated disc (white arrows) but upon translocation it is detected laterally of the membrane. (b) Fluorescence micrographs demonstrate massive translocation of ezrin. Ezrin is part of the cell blebs which are, when occurring to this extent, characteristic for dying cells. (c) Fluorescence micrographs show increases and accumulation of ezrin in cell extensions of IGF-1 stimulated adult cardiomyocytes after seven days. Note that serum shows also some effects on ezrin localization in control cultures (Con). (d) Fluorescence images of oncostatin M receptor-β siRNA treated adult rat cardiomyocytes (OSM + siOβ) in culture demonstrate successful interruption of OSM induced remodeling after 7 days. Con indicates albumin treated control cultures.
Mentions: In order to accelerate the discovery of disease-relevant peptides animal culture models provide “simplified” systems for the analysis on an “omics” platform (Figure 3(a)). Primary cultures of cardiomyocytes are particularly suitable for “omics” studies, since adult cardiomyocytes are terminally differentiated and they transfer their epigenetic, genomic, and proteomic in vivo status into the culture dish, which might not be preserved in cell lines or passaged cells [37]. Primary cultures are, as defined by the Latin term “primus,” cells which are directly used for experiments after isolation from the animal and not further passaged. The strong correlation we demonstrated between differentially regulated proteins of remodeling cardiomyocytes in vivo and in vitro [6, 14, 15] has permitted us to find ERM proteins (Figures 3 and 4) and other potentially relevant candidates [6, 15, 31] in oncostatin M (Figure 2(b)) and IGF-1 (insulin-like growth factor-1) stimulated cultures of adult rat cardiomyocytes.

Bottom Line: Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate.To achieve this, various animal models in combination with an "omics" toolbox can be used.These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.

ABSTRACT
It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an "omics" toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.

No MeSH data available.


Related in: MedlinePlus