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Updated: Jul 9, 2026

In Vitro Model of Coronary Angiogenesis
08:03

In Vitro Model of Coronary Angiogenesis

Published on: March 10, 2020

Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and

Nynke M S van den Akker1, Vincenza Caolo, Lambertus J Wisse

  • 1Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, PO Box 9600, 2300 RC Leiden, The Netherlands.

Cardiovascular Research
|December 21, 2007
PubMed

Insights

Vascular endothelial growth factor (VEGF) isoforms critically influence coronary artery development by modulating the VEGF/Notch/ephrinB2 pathway. Understanding this balance is key to improving cardiac revascularization therapies.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Molecular Signaling

Background:

  • Cardiac revascularization therapies often target the vascular endothelial growth factor (VEGF) pathway, but success has been variable.
  • The precise role of the VEGF/Notch/ephrinB2 cascade in coronary development requires further elucidation to optimize therapeutic strategies.

Purpose of the Study:

  • To investigate the impact of different vascular endothelial growth factor (VEGF) isoforms on coronary development.
  • To explore the involvement of the VEGF/Notch/ephrinB2 signaling cascade in normal and abnormal coronary maturation.
  • To provide insights for enhancing therapeutic interventions targeting VEGF signaling in cardiac conditions.

Main Methods:

  • In vivo studies using Vegf120/120 mouse embryos with immunohistochemistry and RT-qPCR.
  • In vitro experiments treating human arterial coronary endothelial cells with VEGF121 or VEGF165, followed by RT-qPCR.
  • Analysis of arterial and venous marker expression, including Notch1, Delta-like4, ephrinB2, and chicken ovalbumin upstream promoter transcription factor II.

Main Results:

  • Specific VEGF isoforms differentially regulated arterial and venous marker expression in developing coronary endothelium.
  • VEGF165 demonstrated the strongest effect on arterial marker expression in vitro.
  • Abnormal coronary arteriogenesis and medial development were observed in mouse embryos, with altered expression of smooth muscle alpha-actin, Delta-like1, and Notch3.

Conclusions:

  • VEGF isoform-dependent alterations in the VEGF/Notch/ephrinB2 cascade disrupt coronary development.
  • This study highlights the importance of spatiotemporal control of VEGF signaling for proper vascular maturation.
  • Findings can guide the optimization of VEGF-targeted therapies for cardiac revascularization by balancing angiogenesis and maturation.
Abstract

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