肺動脈性肺高血圧症におけるNO-cGMP-PKG Axisの重要性

抄録

Pulmonary arterial hypertension (PAH) is a chronic and life-threatening disease characterised by progressive vascular remodelling that leads to increased pulmonary vascular resistance, right ventricular heart failure and death. PAH is defined by >25 mmHg increase in pulmonary arterial blood pressure and a pulmonary capillary wedge pressure of 15 mmHg. If left untreated PAH is fatal; it has a survival rate of just 34 % after 5 years. Current therapies for PAH include stimulating the nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) axis, improving the prostacyclin pathway or inhibiting the endothelin pathway. Although the causal relationship remains unproven, the NO–sGC–cGMP axis is ultimately a critical factor in the development of PAH because the condition is associated with endothelial dysfunction, impaired NO synthesis and insufficient stimulation of the NO–sGC–cGMP pathway. NO activates sGC, resulting in the synthesis of cGMP, which is a key mediator of pulmonary arterial vasodilatation that may also inhibit vascular smooth muscle proliferation and platelet aggregation. Dysregulation of the NO–sGC–cGMP axis results in pulmonary vascular inflammation, thrombosis and constriction, and ultimately leads to PAH. Therapeutic options targeting the NO–sGC–cGMP axis include phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil and tadalafil, and the sGC stimulator riociguat. In this session, I would like to introduce the importance of NO-cGMP-PKG Axis in PAH and discuss the similarities and differences between PDE5 inhibitors and sGC stimulator and considers which is better for the treatment of PAH.