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0199: Endoglin is required to maintain normal cardiac function in adult life
- Source :
- Archives of Cardiovascular Diseases Supplements. 6
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Endoglin protein (also known as CD105) is a co-receptor for members of the transforming growth factor-β (TGFβ) superfamily of ligands, and regulates angiogenesis. Patients carrying mutations in the endoglin gene develop the inherited vascular dysplasia, Hereditary Haemorrhagic Telangiectasia (HHT). In light of the growing clinical interest in endoglin function in cardiovascular disease, we aimed to determine its role by depleting endoglin in a mouse model during adult life and assess effects on cardiac function. Endoglin was depleted in adult Rosa26-Cre-ERT2;Engfl/fl mice using tamoxifen treatment to generate “ubiquitous” endoglin knockout (Eng-iKOu) mice and cardiac magnetic resonance imaging (MRI) was used to evaluate cardiac function at 1, 3, 5 and 12 weeks after endoglin knockdown. Loss of endoglin leads to an enlarged heart and cardiomyocyte hypertrophy within 5 weeks and left ventricular volumes continued to enlarge substantially over subsequent weeks. However, LV ejection fraction was not significantly altered in Eng-iKOu mice compared with controls suggesting that cardiac function was not impaired. To address whether the cardiac remodelling observed in Eng-iKOu mice was due to loss of endoglin in endothelial cells we used a transgenic Cre line (Cdh5Cre-ERT2) to generate endothelial specific depletion of endoglin (Eng-iKOe). These mice showed a similar increase in heart mass and ventricular volumes to the Eng-iKOu mice. To investigate if vasomotor defects are contributing to the major cardiac remodelling, we analysed vasomotor function in the aortas of Eng-iKOe mice. We found an increased contraction response of the aorta to phenylephrine in Eng-iKOe mice compared to controls, suggesting that endoglin is important in controlling the aortic contractile response. These results describe a novel phenotype and highlight the importance of endothelial endoglin in the maintenance of cardiac structure and function.
- Subjects :
- Cardiac function curve
Aorta
medicine.medical_specialty
Ejection fraction
medicine.diagnostic_test
Angiogenesis
business.industry
Transgene
Endoglin
Endocrinology
Cardiac magnetic resonance imaging
hemic and lymphatic diseases
medicine.artery
Internal medicine
cardiovascular system
otorhinolaryngologic diseases
medicine
business
Cardiology and Cardiovascular Medicine
Transforming growth factor
Subjects
Details
- ISSN :
- 18786480
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Archives of Cardiovascular Diseases Supplements
- Accession number :
- edsair.doi.dedup.....7b08f7bde055dc3475f6cc8954d71f83
- Full Text :
- https://doi.org/10.1016/s1878-6480(14)71377-1