BMP signaling in vascular biology and disease.

Cardiovascular diseases are worldwide the leading cause of mortality (31% of all deaths, WHO) and disability. These diseases include heart failure, coronary artery disease, heart disease, hypertension, cerebrovascular and peripheral vascular diseases. Dysfunction of endothelial cells (ECs) lining the inner wall of the vasculature is a major initiator that fuels the progression of cardiovascular disease. Mutations in genes encoding different components of the bone morphogenetic protein (BMP) pathway cause various severe vascular diseases such as hereditary hemorrhagic telangiectasia, bicuspid aortic valve with thoracic aortic aneurysms and pulmonary arterial hypertension. BMPs are secreted factors that belong to the larger transforming growth factor (TGF)β family. Signaling by BMPs contributes to the morphological, functional and molecular differences ('heterogeneity') among ECs in different vessel types like arteries, veins, lymphatic vessels and in different organs. Understanding how BMP signaling co-regulates EC heterogeneity in homeostasis and how its deregulation can contribute to disease is key to obtain insights in the genesis of vessel-type restricted disorders and design improved disease-tailored therapies with reduced side effects.

Keywords:MOUSE MODELS, MODEL SYSTEMS, GENETIC DISEASE

Disciplines:Vascular diseases

Project type:Collaboration project