PhD defence S. (Siyu) Tian

Dissertation in short:

Pulmonary hypertension (PH) is a disease of the pulmonary vascular system. PH is a life-threatening disease. The current PH treatments principally focus on reducing pulmonary vascular resistance by inducing pulmonary vasodilation and a generalized inhibition of proliferation/mitogenic properties, but do not specifically target inflammatory and pulmonary vascular remodeling. This thesis aimed to investigate the mechanism of pulmonary vascular remodeling and to identify new targets for treatment of  PH patients. In part1, we summarized the role of mechanotransduction in development and progression of PH and specifically investigated the potential involvement of mechanotransduction channel Piezo2. In part 2, a cohort of PH patients with long-term follow-up was analyzed to investigate the prognostic value of metabolites of tryptophan through the kynurenine pathway (KP). Then we found that 1) Piezo2 is a critical factor in endothelial shear stress sensing and subsequent (patho)physiological responses. 2) loss of Piezo2 may contribute to pulmonary vascular remodeling and PH. 3) tryptophan and KP were activated in treatment-naïve PAH patients. 4) lower levels of plasma melatonin were associated with a worse long-term survival in PAH patients.