Drug discovery focused on novel pathogenic proteins for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a fatal disease in which the wall thickening and narrowing of pulmonary microvessels progress due to complicated interactions among processes such as endothelial dysfunction, the proliferation of pulmonary artery smooth muscle cells (PASMCs) and adventitial fibrocytes, and inflammatory cell infiltration. Early diagnosis of patients with PAH is difficult and lung transplantation is the only last choice to save severely ill patients. However, the number of donors is limited. Many patients with PAH show rapid progression and a high degree of pulmonary arterial remodeling characterized by the abnormal proliferation of PASMCs, which makes treatment difficult even with multidrug therapy comprising pulmonary vasodilators. Thus, it is important to develop novel therapy targeting factors other than vasodilation, such as PASMC proliferation. In the development of PAH, inflammation and oxidative stress are deeply involved in its pathogenesis. Excessive proliferation and apoptosis resistance in PASMCs are key mechanisms underlying PAH. Based on those characteristics, we recently screened novel pathogenic proteins and have performed drug discovery targeting those proteins. To confirm the clinical significance of this, we used patient-derived blood samples to evaluate biomarker potential for diagnosis and prognosis. Moreover, we conducted high throughput screening and found several inhibitors of the pathogenic proteins. In this review, we introduce the recent progress on basic and clinical PAH research, focusing on the screening of pathogenic proteins and drug discovery.

Robot-assisted stenting of a high-grade anastomotic pulmonary artery stenosis following single lung transplantation.

PURPOSE: To report robot-assisted stenting of a stenosis at the pulmonary artery anastomosis following lung transplantation, a rare complication that conveys poor prognosis even after surgical correction. TECHNIQUE: The technique is illustrated in a 72-year-old man with end-stage lung disease who received a left single lung transplant. On postoperative day 54, he was evaluated for recurrent dyspnea on exertion that was due to a severe stenosis at the site of the pulmonary artery anastomosis. Balloon angioplasty was performed, and a 10-mm stent was deployed, with marked clinical improvement. Fourteen months later, he presented with recurrent symptoms due to in-stent restenosis. Multiple attempts at catheterization and balloon angioplasty of the stent failed. Due to the technical difficulty involved in maneuvering the balloon while maintaining stability, it was decided to repeat the angioplasty with the assistance of a Hansen Sensei remote robotic navigation system. The robotic arm markedly enhanced stability and facilitated successful navigation of the stented site. A 16-mm-diameter Wallstent was placed through the previously placed balloon-expandable stent and postdilated. CONCLUSION: A remote robotic catheter navigation system was able to assist stenting of an anastomotic pulmonary artery stenosis following failure of conventional interventional techniques.