Reduced angiogenic responses in adult endoglin heterozygous mice

doi:10.1016/j.cardiores.2005.11.020

Cardiovascular Research 2006 69(4):845-854; doi:10.1016/j.cardiores.2005.11.020

This Article

	Full Text
	FREE Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Add to My Personal Archive
	Download to citation manager
	Request Permissions

Google Scholar

	Articles by Jerkic, M.
	Articles by López-Novoa, J. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Jerkic, M.
	Articles by López-Novoa, J. M.

Social Bookmarking

	What's this?

Reduced angiogenic responses in adult endoglin heterozygous mice

Mirjana Jerkic^a^,b^,1, Alicia Rodríguez-Barbero^a^,1, Marta Prieto^a, Mourad Toporsian^b^,d, Miguel Pericacho^a, Juan V. Rivas-Elena^a, Juana Obreo^a, Angela Wang^b, Fernando Pérez-Barriocanal^a, Miguel Arévalo^c, Carmelo Bernabéu^e, Michelle Letarte^b^,d and José M. López-Novoa^a^,*

^aInstituto "Reina Sofía" de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain
^bCancer Research Program, The Hospital for Sick Children, Toronto, Canada M5G1X8
^cDepartmento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain
^dThe Heart and Stroke Lewar Centre of Excellence, University of Toronto, Toronto, Canada
^eCentro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu, 9, 28040 Madrid, Spain

^* Corresponding author. Tel.: +34 923 294 472; fax: +34 923 294 669. Email address: jmlnovoa{at}usal.es

Objective: To determine if angiogenesis is altered in adultEndoglin heterozygous (Eng^+/–) mice, the animal modelfor the vascular disorder hereditary hemorrhagic telangiectasiatype 1 (HHT1).

Methods: Primary cultures of endothelial cells were generatedfrom Eng^+/– and Eng^+/+ mice and analyzed for proliferation,migration, and ability to form capillary-like tubes. Endothelialcells derived from umbilical veins of newborns (HUVEC) withan HHT1 genotype were also tested for capillary formation. Twoin vivo models of angiogenesis were tested in the Eng^+/–and Eng^+/+ mice: Matrigel implant-dependent angiogenesis andreperfusion following hindlimb ischemia.

Results: The Eng^+/– endothelial cells displayed significantlyreduced proliferation and migration, increased collagen production,and decreased NO synthase expression and vascular endothelialgrowth factor (VEGF) secretion. They also showed impaired capillarytube formation in vitro, as did the HHT1 HUVEC. These endothelialcell-specific abnormalities were associated with impaired Matrigel-dependentcapillary tube formation in vivo and delayed reperfusion followinghindlimb ischemia.

Conclusions: Although vascular development is normal in Eng^+/–mice, angiogenic abnormalities were observed in the adult miceand their isolated endothelial cells. These results suggestthat a normal level of endoglin is required for full angiogenicactivity.

KEYWORDS Angiogenesis; Endoglin; HHT1; Nitric oxide; VEGF

¹ These authors contributed equally to the paper.

Time for primary review 21 days

Add to CiteULike CiteULike Add to Connotea Connotea Add to Del.icio.us Del.icio.us What's this?

This article has been cited by other articles:

R. S. Svatek, J. A. Karam, C. G. Roehrborn, P. I. Karakiewicz, K. M. Slawin, and S. F. Shariat
Preoperative Plasma Endoglin Levels Predict Biochemical Progression After Radical Prostatectomy
Clin. Cancer Res., June 1, 2008; 14(11): 3362 - 3366.
[Abstract] [Full Text] [PDF]