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Updated: May 9, 2026
Isolation and Physiological Analysis of Mouse Cardiomyocytes
Published on: September 7, 2014
Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress
Vishnu Chintalgattu1, Di Ai, Robert R Langley
1Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-beta signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-beta was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-beta is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.
Insights
Platelet-derived growth factor receptor (PDGFR)-beta in cardiomyocytes is vital for heart repair under stress. Its deficiency leads to heart failure, offering insights into PDGFR inhibitor cardiotoxicity.
Area of Science:
- Cardiovascular Biology
- Oncology
- Molecular Medicine
Background:
- Platelet-derived growth factor receptor (PDGFR) signaling is a key target in cancer therapy.
- PDGFR inhibitors have been linked to cardiotoxicity, but the underlying mechanisms are unclear.
- The role of PDGFR signaling in cardiac function and stress response is largely unknown.
Purpose of the Study:
- To investigate the role of PDGFR-beta in the heart during stress.
- To elucidate the mechanism by which PDGFR-beta signaling influences cardiac response to stress.
- To explore the implications for PDGFR inhibitor-induced cardiotoxicity.
Main Methods:
- Utilized mouse models with cardiac-specific knockout of Pdgfrb.
- Induced cardiac stress using load-induced models.
- Assessed cardiac function, angiogenesis, and cardiomyocyte signaling pathways.
Main Results:
- PDGFR-beta expression and activation increase in the heart under stress.
- Loss of cardiac PDGFR-beta leads to dysfunction and heart failure following stress.
- Cardiomyocyte PDGFR-beta is essential for stress-induced cardiac angiogenesis and paracrine signaling.
Conclusions:
- Cardiomyocyte PDGFR-beta is a critical regulator of the compensatory cardiac response to pressure overload.
- PDGFR-beta signaling in cardiomyocytes is vital for maintaining heart function during stress.
- These findings provide a mechanistic basis for cardiotoxicity observed with anticancer PDGFR inhibitors.
