Related Experiment Video
Updated: Jul 19, 2026
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Controlling cardiomyocyte survival
Nicolaas de Jonge1, Marie Jose Goumans, Daan Lips
1Department of Cardiology, Heart Lung Center Utrecht, UMC Utrecht, The Netherlands.
Insights
Cardiomyocyte survival pathways, including hypertrophy and apoptosis signaling, are interconnected. Targeting these pathways, like ERK and Akt, can protect heart cells from ischemic damage and preserve cardiac function.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Signaling
Background:
- Signaling pathways for hypertrophy, cell cycle control, apoptosis, and cell survival are increasingly recognized as interconnected.
- Cardiomyocytes have a blocked cell cycle, shifting focus to hypertrophy pathways for ischemic models.
- Understanding cell fate determination by stimuli and microenvironment is crucial.
Purpose of the Study:
- To investigate the protective effects of various interventions on cardiomyocyte loss and function.
- To explore the role of specific signaling pathways, such as MAPK and Akt, in preventing cardiac damage.
- To highlight the importance of assessing both cell death and myocardial function.
Main Methods:
- Review of studies involving growth factors (IGF1, FGF1,2) and downstream signaling interventions.
- Analysis of gene-targeted mouse models with specific pathway activations (e.g., ERK, Akt).
- Emphasis on the need for improved molecular imaging techniques for cardiomyocyte death assessment.
Main Results:
- Growth factors and downstream pathway interventions demonstrate cardiomyocyte protection in vitro and in vivo.
- Constitutive activation of ERK proteins prevents ischemic heart damage and preserves left ventricular function.
- Nuclear Akt plays a key role in preventing apoptosis, supported by genetic and pharmacological evidence.
Conclusions:
- Interventions targeting interconnected signaling pathways offer cardioprotection against ischemic injury.
- ERK and Akt pathways are critical targets for preventing cardiomyocyte loss and maintaining cardiac function.
- Accurate assessment of myocardial function alongside cell death measurement is essential for evaluating adaptive vs. maladaptive responses.
Abstract:
Gradually the distinction between signalling pathways originally believed to be specific for either hypertrophy, cell cycle control, apoptosis and cell survival are fading. The subtle variations in stimuli to a cell and the microenvironment will determine cell fate. In cardiomyocytes the entrance into the cell cycle is efficiently blocked. Therefore attention has focused on pathways involved in hypertrophy to assess effects in ischaemic models and vice versa. Interventions at different levels have been shown to be cardiomyocyte protective. Various growth factors (including IGF1 and FGF1,2) have shown to prevent or delay cardiomyocyte loss in and ex vivo. Similar results have been reported for downstream interventions in the signalling pathways. Strong effects after MAPK activation have been shown in gene targeted mice. Especially constitutive activation of the ERK proteins prevents ischemic damage of the heart with conservation of left ventricular function. Evidence for a key role of nuclear Akt in preventing apoptosis is accumulating from various genetic and pharmacological sources. Development of techniques to measure the level of cardiomyocyte death depends on further improvements in molecular imaging in mouse and human. In addition to studying cardiomyocyte cell death, it is crucial to measure myocardial function. Whether hypertrophy following ischaemia is adaptive or maladaptive and whether all apoptosis is detrimental will have to be determined by assessment of left ventricular function through invasive and noninvasive methods.
