Pulmonary vascular diseases have a multifactorial pathobiology, characterised by abnormalities of the smooth muscle, advential and endothelial cells which result in an obliterative remodelling of the pulmonary circulation, occlusion of the lumen in medium-sized and small pulmonary arteries due to excessive vasoconstriction, cellular proliferation and reduced apoptosis in the vascular wall and in situ thrombosis, as well as reduction in the number of pulmonary vessels. As a result, right ventricular afterload increases, leading to right heart failure and premature death. There has recently been a shift in treatment paradigm, from vasodilatory to anti-remodelling and even “reverse-remodelling” therapeutic strategies, as new evidence suggests that the proliferative and antiapoptotic environment in the vascular wall of medium and small pulmonary arteries shares some features with neoplasia. Deciphering the molecular and cellular mechanisms underlying the pathobiology of pulmonary vascular remodelling, such as cytoskeletal reorganisation, dysregulation of cell growth and transcription factors and abnormal cell proliferation are the aims of this program line.
- Deciphering the molecular pathways leading to vascular remodelling
- Regulation of ion channels and calcium signalling homeostasis in pulmonary vascular development and in vascular remodelling
- Post-translational modification of ion channels in pulmonary vascular remodelling