Intercellular Signaling in Cardiovascular Development and Disease

Cardiovascular Biology and Cardiovascular Diseases
Centro Nacional de Investigaciones Cardiovasculares "Carlos III" (CNIC)

We are interested in the molecular mechanisms that regulate cardiovascular development, homeostasis and disease. Most of our effort centers on the study of the Notch pathway.

Notch pathway is involved in many processes during vertebrate cardiac development and disease. Our work over the last year focused on the role of Notch as a promoter of cardiac valve formation. We found that Notch activity in the endocardium—the inner endothelial lining of the heart—intersects with a myocardial signal, Bmp2, to activate a mesenchymal gene program that results in the formation of the valve primordia. Our work in this area has characterized the interplay between endocardium and myodcardium that underlies the role of Notch in this process.

We are currently conducting imaging and functional studies to define the expression and function of Notch in epicardium and coronary vessel development and to explore how the interplay between different Notch ligands and receptors generates signal specificity during chamber development. These studies are complemented by genetic manipulation of zebrafish to examine the role in heart and fin regeneration of Notch and other molecules identified in genomic screens.

For our work on the adult heart we have established a pioneering mouse model of aortic valve stenosis, which we are using to study the role of Notch in this disease in combination with mouse genetics, cell culture and analysis of human pathological samples. In the future we plan to conduct similar studies with other carefully engineered mouse models, and to incorporate genetic and epidemiologic studies in patients. These studies will provide a clearer understanding of the molecular mechanisms underlying of the contribution of altered Notch signaling to neonatal and adult cardiac disease.

Biomolecules & Cell D.
Molecular Biomedicine