Cooperation between VEGF and β3 integrin during cardiac vascular development

• Published in: Blood Vol. 109; no. 5; pp. 1962 - 1970
• Main Authors: Weis, Sara M., Lindquist, Jeffrey N., Barnes, Leo A., Lutu-Fuga, Kimberly M., Cui, Jianhua, Wood, Malcolm R., Cheresh, David A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.03.2007; The Americain Society of Hematology; American Society of Hematology
• Series: Hemostasis, Thrombosis, and Vascular Biology
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Hemostasis, Thrombosis, and Vascular Biology; Medical sciences; Heart; Vascular endothelium growth factor; β3 integrin; Hematology; Cooperation; Blood vessel; Circulatory system
• DOI: 10.1182/blood-2005-10-038893
• ISSN: 0006-4971

In the developing myocardium, vascular endothelial growth factor (VEGF)–dependent neovascularization occurs by division of existing vessels, a process that persists for several weeks following birth. During this remodeling phase, mRNA expression of β3 integrin in the heart decreases significantly as vessel maturation progresses. However, in male mice lacking β3, coronary capillaries fail to mature and continue to exhibit irregular endothelial thickness, endothelial protrusions into the lumen, and expanded cytoplasmic vacuoles. Surprisingly, this phenotype was not seen in female β3-null mice. Enhanced VEGF signaling contributes to the β3-null phenotype, because these vessels can be normalized by inhibitors of VEGF or Flk-1. Moreover, intravenous injection of VEGF induces a similar angiogenic phenotype in hearts of adult wild-type mice. These findings show a clear vascular phenotype in the hearts of mice lacking β3 and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF.