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Updated: Feb 18, 2026
Analysis of Coronary Vessels in Cleared Embryonic Hearts
Published on: December 7, 2016
Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial
Shota Kurotsu1, Rina Osakabe1, Mari Isomi2
1Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Insights
This study reveals the distinct expression patterns of vascular endothelial growth factor (VEGF) receptors Flk1 and Flt1 in coronary vessels during heart development and after myocardial infarction (MI). Understanding these patterns is key for coronary angiogenesis research.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Angiogenesis Research
Background:
- The coronary vascular system is vital for heart function, but the molecular regulation of its growth (angiogenesis) is not fully understood.
- Vascular Endothelial Growth Factor (VEGF) signaling, via receptors Flk1 and Flt1, is crucial for angiogenesis, yet their specific roles and expression in the heart vasculature are largely unknown.
- Lack of specific antibodies has hindered the study of Flk1 and Flt1 expression in coronary vessels.
Purpose of the Study:
- To determine the spatiotemporal expression patterns of Flk1 and Flt1 in mouse coronary vasculature.
- To investigate how Flk1 and Flt1 expression changes during normal cardiac development.
- To examine Flk1 and Flt1 expression dynamics in response to myocardial infarction (MI).
Main Methods:
- Utilized multiple genetically engineered mouse models (reporter mice) including Flk1-GFP, Flk1-LacZ, Flt1-DsRed, and double transgenic lines.
- Analyzed expression patterns in neonatal and adult mouse hearts.
- Examined expression changes in the heart at various time points after experimentally induced myocardial infarction (MI).
Main Results:
- Flk1 exhibited a transmural gradient in neonatal ventricles, decreasing in adult coronary vessels.
- Flt1 showed homogeneous expression in neonatal and adult coronary endothelial cells.
- Both Flk1 and Flt1 were induced in regenerating vessels post-MI, with Flk1 downregulated and Flt1 maintained, mirroring developmental expression.
- This is the first study to map Flk1 and Flt1 expression in the coronary vasculature during development and post-MI.
Conclusions:
- Flk1 and Flt1 display distinct spatiotemporal expression patterns in the coronary vasculature.
- These differential expression patterns suggest unique and significant roles for Flk1 and Flt1 in coronary angiogenesis.
- The findings provide a foundation for further research into VEGF receptor function in cardiac vascular development and repair.
Abstract:
The coronary vascular system is critical for myocardial growth and cardiomyocyte survival. However, the molecular mechanism regulating coronary angiogenesis remains elusive. Vascular endothelial growth factor (VEGF) regulates angiogenesis by binding to the specific receptors Flk1 and Flt1, which results in different functions. Despite the importance of Flk1 and Flt1, their expression in the coronary vasculature remains largely unknown due to the lack of appropriate antibodies for immunostaining. Here, we analyzed multiple reporter mice including Flk1-GFP BAC transgenic (Tg), Flk1-LacZ knock-in, Flt1-DsRed BAC Tg, and Flk1-GFP/Flt1-DsRed double Tg animals to determine expression patterns in mouse hearts during cardiac growth and after myocardial infarction (MI). We found that Flk1 was expressed in endothelial cells (ECs) with a pattern of epicardial-to-endocardial transmural gradients in the neonatal mouse ventricle, which was downregulated in adult coronary vessels with development. In contrast, Flt1 was homogeneously expressed in the ECs of neonatal mouse hearts and expression was maintained until adulthood. After MI, expression of both Flk1 and Flt1 was induced in the regenerating coronary vessels at day 7. Intriguingly, Flk1 expression was downregulated thereafter, whereas Flt1 expression was maintained in the newly formed coronary vessels until 30 days post-MI, recapitulating their expression kinetics during development. This is the first report demonstrating the spatiotemporal expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after MI; thus, this study suggests that these factors have distinct and important functions in coronary angiogenesis.
