Checkpoint Kinase 1 Promotes the Development of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is characterized by histological changes in the distal pulmonary arteries, perivascular inflammation and fibrotic change, and right ventricular failure.1–5 In addition to genetic backgrounds, many environmental factors as well as volume overload because of heart disease and inflammation are involved in the development of PAH.6–8 In this process, pulmonary artery smooth muscle cells (PASMCs) will suffer epigenetic modifications by transcriptional factors.9,10 Recently, we have reported that SeP (selenoprotein P) is a pathogenic protein that induces the production of reactive oxygen species and promotes the proliferation of PAH-PASMCs (Figure).9–11 Moreover, it has been demonstrated that excessive reactive oxygen species (oxidative stress) will induce DNA damage in PAH-PASMCs.12–14 The characteristics of PASMCs in patients with PAH (PAH-PASMCs) are different from those of healthy controls.9,15 The abnormal features of PAH-PASMCs are based on their altered cellular functions similar to cancer cells.2,13 Thus, these features of PAH-PASMCs can potentially be a target to cure patients with PAH.