Title: Inactivation of Smad5 in endothelial cells and smooth muscle cells demonstrates that Smad5 is required for cardiac homeostasis
Authors: Umans, Lieve
Cox, Luk
Tjwa, Marc
Bito, Virginie
Vermeire, Liesbeth
Laperre, Kjell
Sipido, Karin
Moons, Lieve
Huylebroeck, Danny
Zwijsen, An # ×
Issue Date: 9-Apr-2007
Series Title: American Journal of Pathology vol:170 issue:5 pages:1460-1472
Abstract: Smads are intracellular signaling proteins that transduce signals elicited by members of the transforming growth factor (TGF)-beta superfamily. Smad5 and Smad1 are highly homologous, and they mediate primarily bone morphogenetic protein (Bmp) signals. We used the Cre-loxP system and Sm22-Cre and Tie-1-Cre mice to study the function of Smad5 in the developing blood vessel wall. Analysis of embryos demonstrated that deletion of Smad5 in endothelial or smooth muscle cells resulted in a normal organization of embryonic and extra-embryonic vasculature. Angiogenic assays performed in adult mice revealed that mutant mice display a comparable angiogenic and vascular remodeling response to control mice. In Sm22-Cre; Smad5(fl/-) mice, Smad5 is also deleted in cardiomyocytes. Echocardiographic analysis on those 9-month-old female mice demonstrated larger left ventricle internal diameters and decreased fractional shortening compared with control littermates without signs of cardiac hypertrophy. The decreased cardiac contractility was associated with a decreased performance in a treadmill experiment. In isolated cardiomyocytes, fractional shortening was significantly reduced compared with control cells. These data demonstrate that restricted deletion of Smad5 in the blood vessel wall results in viable mice. However, loss of Smad5 in cardiomyocytes leads to a mild heart defect.
ISSN: 0002-9440
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Molecular Biology (Celgen) (-)
Vesalius Research Centre (-)
Experimental Cardiology
Clinical and Experimental Endocrinology
Molecular and Vascular Biology
Embryo and Stemcells (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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