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Updated: Apr 14, 2026
In Vivo Imaging of Transduction Efficiencies of Cardiac Targeting Peptide
Published on: June 11, 2020
In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease
Julia U Sprenger1, Ruwan K Perera1, Julia H Steinbrecher2
11] Emmy Noether Group of the DFG, European Heart Research Institute Göttingen, University Medical Center Göttingen, D-37075 Göttingen, Germany [2] Department of Cardiology and Pulmonology, Heart Research Center Göttingen, University Medical Center Göttingen, Georg August University, D-37075 Göttingen, Germany [3] Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
Abstract:
3',5'-cyclic adenosine monophosphate (cAMP) is an ubiquitous second messenger that regulates physiological functions by acting in distinct subcellular microdomains. Although several targeted cAMP biosensors are developed and used in single cells, it is unclear whether such biosensors can be successfully applied in vivo, especially in the context of disease. Here, we describe a transgenic mouse model expressing a targeted cAMP sensor and analyse microdomain-specific second messenger dynamics in the vicinity of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). We demonstrate the biocompatibility of this targeted sensor and its potential for real-time monitoring of compartmentalized cAMP signalling in adult cardiomyocytes isolated from a healthy mouse heart and from an in vivo cardiac disease model. In particular, we uncover the existence of a phosphodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced β-adrenergic receptor-cAMP signalling to SERCA.
Insights
Researchers developed a new transgenic mouse model to track cyclic adenosine monophosphate (cAMP) signaling in real-time within heart cells. This tool revealed impaired cAMP signaling in cardiac disease, offering insights into cardiovascular health.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Biomedical Engineering
Background:
- Cyclic adenosine monophosphate (cAMP) is a crucial second messenger regulating cellular functions in specific microdomains.
- Existing cAMP biosensors are primarily used in single cells, with limited in vivo application, especially in disease contexts.
- Understanding compartmentalized cAMP dynamics is vital for deciphering physiological regulation and disease mechanisms.
Purpose of the Study:
- To develop and validate a transgenic mouse model for in vivo monitoring of microdomain-specific cAMP signaling.
- To investigate the role of cAMP signaling in the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) vicinity.
- To analyze alterations in cAMP dynamics within a cardiac disease model.
Main Methods:
- Generation of a transgenic mouse model expressing a targeted cAMP biosensor.
- Isolation and analysis of adult cardiomyocytes from healthy and diseased mouse hearts.
- Real-time monitoring of cAMP dynamics in subcellular microdomains, particularly near SERCA.
- Assessment of biosensor biocompatibility and signal fidelity in vivo.
Main Results:
- The developed cAMP biosensor is biocompatible and suitable for real-time, in vivo monitoring of compartmentalized cAMP signaling.
- Microdomain-specific cAMP dynamics near SERCA were successfully analyzed in both healthy and diseased cardiomyocytes.
- A phosphodiesterase-dependent communication pathway between receptors and microdomains was identified.
- This pathway is impaired in cardiac hypertrophy, leading to reduced beta-adrenergic receptor-cAMP signaling to SERCA.
Conclusions:
- The transgenic cAMP sensor mouse model provides a powerful tool for studying in vivo, compartmentalized second messenger signaling.
- Cardiac hypertrophy disrupts specific cAMP signaling pathways crucial for normal cardiac function.
- These findings offer new insights into the molecular mechanisms underlying cardiac disease and potential therapeutic targets.
