Pulmonary arterial hypertension (PAH) causes the life-threatening right heart failure. Despite intensive research, the pathogenesis of PAH is still largely unknown, the early diagnosis is difficult and the efficient treatment is lacking. Due to specific oxygen-sensing mechanisms existing in pulmonary arterial bed, the acute hypoxia results in vasoconstriction, while the chronic hypoxia causes additional irreversible vascular remodelling. Recent studies suggest that redox-active signalling species such as reactive oxygen (ROS) play critical role both in vasoconstriction and structural changes in pulmonary artery (PA). Consequently, my studies focus on the new redox-related mechanisms in PA during the course of disease development in mouse/rat models of hypoxia- or monocrotaline-induced PAH, as well as in human PA vascular cells. We recently demonstrated an original new signalling pathway such as negative regulation of the endothelial relaxation by the smooth muscle which could also be of great interest in PAH. Indeed, our data suggested the role of myoendothelial junctions (connexins) in transferring of ROS from vascular smooth muscle cells to endothelium, leading to NO neutralization in PAH. Pharmacological compounds as well as siRNA and knockout mice strategies are used to modify the connexin expression pattern and to address the proliferation of PA smooth muscle and endothelial cells as well as contractile properties of PA in PAH.
Altogether, we believe that such knowledge on (1) ROS as a key player in the crosstalk between PA endothelial and smooth muscle cells via myoendothelial junctions and (2) ROS/growth factors interplays is needed for development of innovative therapies for PAH.