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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

End-systolic midventricular short axis and long axis MRI frames of healthy and failing hearts from humans and mice. (a) MRI images from a healthy control (Con) and patients with aortic stenosis (HT), myocardial infarction (MI), and idiopathic dilated cardiomyopathy (DCM). (b) MRI images from mice 4 weeks after transaortic constriction (HT), 3 weeks after LAD ligation (LAD), and 6-month-old mice with a cardiac restricted overexpression of MCP-1 (iDCM). A healthy control animal is also shown (Con). Note the increase in size and ventricular mass of HT hearts while increases in heart size after MI and after development of (i) DCM are associated with ventricular thinning. Explanations are given in the text. (c) Electron microscopy pictures show different degrees of sarcomeric degeneration in patients with dilated cardiomyopathy (Con versus DCM1 and DCM2; EF < 30%). Human MRI images and electron micrographs were kindly provided by Professor Georg Bachmann and by Dr. Viktoria Polyakova, respectively. Mouse MRI images are adapted and modified from the “Venia legendi” work of J. Pöling.
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fig1: End-systolic midventricular short axis and long axis MRI frames of healthy and failing hearts from humans and mice. (a) MRI images from a healthy control (Con) and patients with aortic stenosis (HT), myocardial infarction (MI), and idiopathic dilated cardiomyopathy (DCM). (b) MRI images from mice 4 weeks after transaortic constriction (HT), 3 weeks after LAD ligation (LAD), and 6-month-old mice with a cardiac restricted overexpression of MCP-1 (iDCM). A healthy control animal is also shown (Con). Note the increase in size and ventricular mass of HT hearts while increases in heart size after MI and after development of (i) DCM are associated with ventricular thinning. Explanations are given in the text. (c) Electron microscopy pictures show different degrees of sarcomeric degeneration in patients with dilated cardiomyopathy (Con versus DCM1 and DCM2; EF < 30%). Human MRI images and electron micrographs were kindly provided by Professor Georg Bachmann and by Dr. Viktoria Polyakova, respectively. Mouse MRI images are adapted and modified from the “Venia legendi” work of J. Pöling.

Mentions: Under physiological workload all cardiac cavities are maintained in a “status quo” (Figure 1(a), Con). Increases in workload might be tolerated by a balanced enlargement of the heart until the workload exceeds the physiological cardiac capability to respond appropriately. Then cardiac remodeling is initiated and alterations of the cellular and extracellular protein composition turn into a major burden disturbing the structure-function relationship (Figures 4(a) and 4(b)). As a consequence alterations in the protein composition cause changes in hemodynamic load and vice versa. Patients with aortic stenosis show an increase in the thickness of the left ventricular wall, and the heart appears to be enlarged with an overall progression in mass of the ventricle and septum (Figure 1(a), HT). When the load is persistent the heart might undergo an irreversible decompensation and dilation [8, 21]. Myocardial structural changes observed in patients with aortic stenosis can be mimicked in a mouse model of transversal aortic constriction [20, 22]. Within the first three weeks the heart develops compensatory hypertrophy (Figure 1(b), HT), and if the heart is not released from hemodynamic overload, as seen in human patients, the chronic maladaptive response leads to cardiac dilation (Figure 1(a), HT) and potentially HF.


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)

End-systolic midventricular short axis and long axis MRI frames of healthy and failing hearts from humans and mice. (a) MRI images from a healthy control (Con) and patients with aortic stenosis (HT), myocardial infarction (MI), and idiopathic dilated cardiomyopathy (DCM). (b) MRI images from mice 4 weeks after transaortic constriction (HT), 3 weeks after LAD ligation (LAD), and 6-month-old mice with a cardiac restricted overexpression of MCP-1 (iDCM). A healthy control animal is also shown (Con). Note the increase in size and ventricular mass of HT hearts while increases in heart size after MI and after development of (i) DCM are associated with ventricular thinning. Explanations are given in the text. (c) Electron microscopy pictures show different degrees of sarcomeric degeneration in patients with dilated cardiomyopathy (Con versus DCM1 and DCM2; EF < 30%). Human MRI images and electron micrographs were kindly provided by Professor Georg Bachmann and by Dr. Viktoria Polyakova, respectively. Mouse MRI images are adapted and modified from the “Venia legendi” work of J. Pöling.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508378&req=5

fig1: End-systolic midventricular short axis and long axis MRI frames of healthy and failing hearts from humans and mice. (a) MRI images from a healthy control (Con) and patients with aortic stenosis (HT), myocardial infarction (MI), and idiopathic dilated cardiomyopathy (DCM). (b) MRI images from mice 4 weeks after transaortic constriction (HT), 3 weeks after LAD ligation (LAD), and 6-month-old mice with a cardiac restricted overexpression of MCP-1 (iDCM). A healthy control animal is also shown (Con). Note the increase in size and ventricular mass of HT hearts while increases in heart size after MI and after development of (i) DCM are associated with ventricular thinning. Explanations are given in the text. (c) Electron microscopy pictures show different degrees of sarcomeric degeneration in patients with dilated cardiomyopathy (Con versus DCM1 and DCM2; EF < 30%). Human MRI images and electron micrographs were kindly provided by Professor Georg Bachmann and by Dr. Viktoria Polyakova, respectively. Mouse MRI images are adapted and modified from the “Venia legendi” work of J. Pöling.
Mentions: Under physiological workload all cardiac cavities are maintained in a “status quo” (Figure 1(a), Con). Increases in workload might be tolerated by a balanced enlargement of the heart until the workload exceeds the physiological cardiac capability to respond appropriately. Then cardiac remodeling is initiated and alterations of the cellular and extracellular protein composition turn into a major burden disturbing the structure-function relationship (Figures 4(a) and 4(b)). As a consequence alterations in the protein composition cause changes in hemodynamic load and vice versa. Patients with aortic stenosis show an increase in the thickness of the left ventricular wall, and the heart appears to be enlarged with an overall progression in mass of the ventricle and septum (Figure 1(a), HT). When the load is persistent the heart might undergo an irreversible decompensation and dilation [8, 21]. Myocardial structural changes observed in patients with aortic stenosis can be mimicked in a mouse model of transversal aortic constriction [20, 22]. Within the first three weeks the heart develops compensatory hypertrophy (Figure 1(b), HT), and if the heart is not released from hemodynamic overload, as seen in human patients, the chronic maladaptive response leads to cardiac dilation (Figure 1(a), HT) and potentially HF.

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