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Updated: Jul 7, 2026
In Vitro Model of Coronary Angiogenesis
Published on: March 10, 2020
Novel tool to suppress cell proliferation in vivo demonstrates that myocardial and coronary vascular growth represent
Kory J Lavine1, Gregory J Schmid, Craig S Smith
1Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract:
Cell proliferation, differentiation, and vascular growth are coordinated processes that are essential for embryonic development, tissue repair, and disease pathogenesis. Of interest, whether these critical processes are dependent upon each other has not been thoroughly explored. We have generated mice that conditionally express the cell cycle inhibitor p27(Kip1), following Cre-mediated recombination, as a tool to separate tissue proliferation from other cellular processes. Using the embryonic heart as a model, we show that myocardial proliferation and coronary development are genetically separable processes. Forced expression of p27, in both a wild-type and in a genetically sensitized background, resulted in ventricular hypoplasia without having any substantial effects on coronary development. We further demonstrate that Hedgehog signaling, which is essential for coronary vascular growth, does not control myocardial proliferation. Together, these studies strongly suggest that myocardial cell proliferation and coronary development are genetically separable programs exemplifying one of the many potential uses of this genetic tool.
Insights
Myocardial proliferation and coronary development are distinct processes. Genetic tools show that inhibiting cell cycle inhibitor p27 causes heart hypoplasia but does not affect coronary growth.
Area of Science:
- Developmental biology
- Cardiovascular research
- Cell cycle regulation
Background:
- Cell proliferation, differentiation, and vascular growth are crucial for embryonic development and tissue repair.
- The interdependence of these processes, particularly in the context of heart development, remains incompletely understood.
Purpose of the Study:
- To investigate whether myocardial proliferation and coronary vascular development are genetically separable processes.
- To utilize a novel genetic tool for dissecting proliferation from other cellular functions in the embryonic heart.
Main Methods:
- Generation of transgenic mice with inducible expression of the cell cycle inhibitor p27(Kip1) via Cre-mediated recombination.
- Analysis of embryonic heart development, focusing on myocardial cell proliferation and coronary vessel formation.
- Assessment of Hedgehog signaling pathways in relation to myocardial proliferation.
Main Results:
- Conditional expression of p27(Kip1) led to significant ventricular hypoplasia, indicating impaired myocardial proliferation.
- Coronary development remained largely unaffected by the forced expression of p27(Kip1).
- Hedgehog signaling, crucial for coronary growth, was found not to regulate myocardial proliferation.
Conclusions:
- Myocardial cell proliferation and coronary development represent genetically separable programs.
- The developed genetic tool provides a valuable method for distinguishing proliferation from other developmental processes.
- These findings offer insights into the coordinated but distinct mechanisms governing heart development.
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