Background: Prolactin (PRL) has been reported to related with cardiovascular and metabolic risk profiles. However, whether it plays a role in pulmonary arterial hypertension (PAH) remains unclear.

Aim: To examine the impact of PRL with PAH, and the function of pulmonary microvascular endothelin cells (PMECs).

Methods: Serum PRL levels were prospectively collected in 406 PAH patients and 285 controls between 2008 to 2019. All patients were followed up for all-cause death. In vitro, hypoxia-induced PMECs were treated by recombinant PRL.

Results: Serum PRL was significant higher in PAH patients compared to controls (314.0 [202.0, 477.0] vs 232.0 [170.5, 339.9] ng/ml; p<0.001), while increased in the patients who did not have severe PAH. During a median time of 7.25 years follow-up, 163 deaths occurred (40.1%). Kaplan-Meier survival curves showed a worse survival rate in the lower tertile comparing to the middle and higher tertile (p for trend=0.007, lower tertile, <239 mIU/mL; middle tertile, 239~415 mIU/mL; and higher tertile, >415 mIU/mL). Patients in the lower tertile had 1.68 times higher risk of death compared with patients in higher tertile (p=0.006) in total patients. This association were more obvious in males (hazard ratio [HR]: 1.98; p=0.03) than females (HR: 1.51; p=0.08). Further multi-factor adjustments did not change the correlation. In vitro, recombinant PRL showed obvious inhibition on proliferation and apoptosis resistance in hypoxia-induce PMECs.

Conclusion: Plasma PRL levels were elevated in PAH patients, exhibit positive association with survival of PAH patients, the mechanism is probably related to anti-proliferation and pro-apoptosis function of PRL in PMECs.