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Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing.

Hermans KC, Daskalopoulos EP, Blankesteijn WM - Fibrogenesis Tissue Repair (2012)

Bottom Line: Wnt signaling plays an important role in embryonic myocardial development but in the adult heart the pathway is thought to be silent.However, there is increasing evidence that components of the Wnt pathway are re-expressed during cardiac repair, implying a regulatory role.Recently, several studies have been published where the effect of interventions in Wnt signaling on infarct healing has been studied.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, 50 Universiteitssingel, 6229ER Maastricht, PO Box 616 6200MD, Maastricht, The Netherlands. wm.blankesteijn@maastrichtuniversity.nl.

ABSTRACT
Following myocardial infarction, wound healing takes place in the infarct area where the non-viable cardiac tissue is replaced by a scar. Inadequate wound healing or insufficient maintenance of the extracellular matrix in the scar can lead to excessive dilatation of the ventricles, one of the hallmarks of congestive heart failure. Therefore, it is important to better understand the wound-healing process in the heart and to develop new therapeutic agents that target the infarct area in order to maintain an adequate cardiac function. One of these potential novel therapeutic targets is Wnt signaling. Wnt signaling plays an important role in embryonic myocardial development but in the adult heart the pathway is thought to be silent. However, there is increasing evidence that components of the Wnt pathway are re-expressed during cardiac repair, implying a regulatory role. Recently, several studies have been published where the effect of interventions in Wnt signaling on infarct healing has been studied. In this review, we will summarize the results of these studies and discuss the effects of these interventions on the different cell types that are involved in the wound healing process.

No MeSH data available.


Related in: MedlinePlus

Potential targets of modulations in Wnt signaling to improve cardiac repair. Interventions in Wnt/Frizzled signaling can modulate several processes such as neovascularization, myofibroblast differentiation and stem cell proliferation/differentiation, which can all contribute to improved healing of the scar, preservation of cardiac function and thereby prevent development of congestive heart failure (CHF).
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Figure 2: Potential targets of modulations in Wnt signaling to improve cardiac repair. Interventions in Wnt/Frizzled signaling can modulate several processes such as neovascularization, myofibroblast differentiation and stem cell proliferation/differentiation, which can all contribute to improved healing of the scar, preservation of cardiac function and thereby prevent development of congestive heart failure (CHF).

Mentions: The wound-healing phase is a critical process for the clinical outcome of patients who have suffered from MI. Abnormal remodeling will result in a poorly healed scar that can cause dilatation of the left ventricle and ultimately progresses into CHF, which can be lethal. Since an increasing number of patients are affected by this problem, it is of major importance that therapeutic interventions do not just delay the progression, but rather prevent the development of CHF. The Wnt/Frizzled pathway is involved in many aspects of cardiac repair following MI and may be a promising therapeutic site for interventions. However, the precise targets and mechanism of intervention are still a matter of debate. Thus far, promising tools have been used in experimental settings, targeting Wnt/Frizzled signaling at several important sites involved in infarct healing such as (myo)fibroblasts, progenitor cells, neovascularization, inflammation, collagen maturation and several others that can contribute to an improved cardiac phenotype by minimizing the scar and reducing ventricular dilatation (Figure2). Wnt/Frizzled signaling is mostly silent under physiological conditions but its components can be upregulated in a pathological state. Because this upregulation is only taking place in the affected organ, pharmacological tools display a relative selectivity at this site, thereby not affecting other systems or organs. Therefore, development of strategies that modulate Wnt/Frizzled signaling can serve as novel therapeutic tools to improve infarct healing and quality of life in patients that have had a MI.


Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing.

Hermans KC, Daskalopoulos EP, Blankesteijn WM - Fibrogenesis Tissue Repair (2012)

Potential targets of modulations in Wnt signaling to improve cardiac repair. Interventions in Wnt/Frizzled signaling can modulate several processes such as neovascularization, myofibroblast differentiation and stem cell proliferation/differentiation, which can all contribute to improved healing of the scar, preservation of cardiac function and thereby prevent development of congestive heart failure (CHF).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472244&req=5

Figure 2: Potential targets of modulations in Wnt signaling to improve cardiac repair. Interventions in Wnt/Frizzled signaling can modulate several processes such as neovascularization, myofibroblast differentiation and stem cell proliferation/differentiation, which can all contribute to improved healing of the scar, preservation of cardiac function and thereby prevent development of congestive heart failure (CHF).
Mentions: The wound-healing phase is a critical process for the clinical outcome of patients who have suffered from MI. Abnormal remodeling will result in a poorly healed scar that can cause dilatation of the left ventricle and ultimately progresses into CHF, which can be lethal. Since an increasing number of patients are affected by this problem, it is of major importance that therapeutic interventions do not just delay the progression, but rather prevent the development of CHF. The Wnt/Frizzled pathway is involved in many aspects of cardiac repair following MI and may be a promising therapeutic site for interventions. However, the precise targets and mechanism of intervention are still a matter of debate. Thus far, promising tools have been used in experimental settings, targeting Wnt/Frizzled signaling at several important sites involved in infarct healing such as (myo)fibroblasts, progenitor cells, neovascularization, inflammation, collagen maturation and several others that can contribute to an improved cardiac phenotype by minimizing the scar and reducing ventricular dilatation (Figure2). Wnt/Frizzled signaling is mostly silent under physiological conditions but its components can be upregulated in a pathological state. Because this upregulation is only taking place in the affected organ, pharmacological tools display a relative selectivity at this site, thereby not affecting other systems or organs. Therefore, development of strategies that modulate Wnt/Frizzled signaling can serve as novel therapeutic tools to improve infarct healing and quality of life in patients that have had a MI.

Bottom Line: Wnt signaling plays an important role in embryonic myocardial development but in the adult heart the pathway is thought to be silent.However, there is increasing evidence that components of the Wnt pathway are re-expressed during cardiac repair, implying a regulatory role.Recently, several studies have been published where the effect of interventions in Wnt signaling on infarct healing has been studied.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, 50 Universiteitssingel, 6229ER Maastricht, PO Box 616 6200MD, Maastricht, The Netherlands. wm.blankesteijn@maastrichtuniversity.nl.

ABSTRACT
Following myocardial infarction, wound healing takes place in the infarct area where the non-viable cardiac tissue is replaced by a scar. Inadequate wound healing or insufficient maintenance of the extracellular matrix in the scar can lead to excessive dilatation of the ventricles, one of the hallmarks of congestive heart failure. Therefore, it is important to better understand the wound-healing process in the heart and to develop new therapeutic agents that target the infarct area in order to maintain an adequate cardiac function. One of these potential novel therapeutic targets is Wnt signaling. Wnt signaling plays an important role in embryonic myocardial development but in the adult heart the pathway is thought to be silent. However, there is increasing evidence that components of the Wnt pathway are re-expressed during cardiac repair, implying a regulatory role. Recently, several studies have been published where the effect of interventions in Wnt signaling on infarct healing has been studied. In this review, we will summarize the results of these studies and discuss the effects of these interventions on the different cell types that are involved in the wound healing process.

No MeSH data available.


Related in: MedlinePlus