CDC2 Is an Important Driver of Vascular Smooth Muscle Cell Proliferation via FOXM1 and PLK1 in Pulmonary Arterial Hypertension

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. mechanism which two proteins direct aberrant not clear. Herein, we identify cyclin-dependent kinase 1 (CDK1), also termed cell division cycle protein 2 (CDC2), as having a primary role promoting progress leading to HPASMC. HPASMC obtained PAH arteries Sugen/hypoxia rats were investigated for their expression CDC2. Protein levels CDC2 much higher than normal donors. Knocking down or with siRNA pharmacological inhibitors lowered cellular considerably. However, knockdown inhibiting its activity RO-3306 did reduce PLK1. Expression reached maximum at G1/S, while G2/M phase cycle. other CDKs such CDK2, CDK4, CDK6, CDK7, CDK9 change Moreover, inhibition via Wee1 inhibitor adavosertib siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, CDC25C led dramatic decreases expression. Lastly, found RNA level be during disease progression rats. In sum, our present results illustrate that increased leads directly resulting potentiated hyperactivity PASMC hypertension. Our further suggest regulation CDC2, associated regulatory proteins, will prove beneficial treatment this disease.