Abstract

It has become clear that signaling by bone morphogenetic proteins (BMPs), which have a long history of studies in bone and early heart development, are also essential for regulating vascular function. Indeed, loss-of-function mutations that cause deregulated BMP signaling are linked to two distinct human vascular syndromes, hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH). PAH involves obstructive remodeling of pulmonary arteries progressing to right heart failure, while HHT results in mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs) in various organs, such as the liver, lungs, gastrointestinal tract, or brain.

Although HPAH and HHT exhibit different clinical manifestations, they share genetic mutations in BMP /TGFβ signaling pathway-related genes. The factors determining whether these mutations lead to HPAH , HHT, or both remain unknown, as do the cellular mechanisms driving each syndrome. In this lecture, the pivotal role of BMPs in the cardiovascular system will be discussed obtained using cells in cell culture and mouse models, as well as the development of an ex vivo heart culture system to model and manipulate TGF β/BMP signaling during cardiac fibrosis.