[Expression of PAI-2 mRNA in peripheral blood leucocytes and regulation by sGC activator in pulmonary hypertension].

OBJECTIVE: To investigate the mRNA expression level of plasminogen activator inhibitor-2 (PAI-2) in peripheral blood leucocytes and regulation by soluble guanylate cyclase (sGC) activator in pulmonary hypertension.

METHODS: The human pulmonary arterial smooth muscle cells were treated with sGC activator Cinaciguat. The mRNA and protein expression levels of PAI-2 were detected with Real-time PCR and Western blot. The fresh blood samples of 8 patients with pulmonary arterial hypertension (PAH) (collected at the China-Japan Friendship Hospital from November 2014 to March 2015), 16 patients with chronic thromboembolic pulmonary hypertension (CTEPH) (collected at the China-Japan Friendship Hospital from November 2014 to March 2015), 24 age- and gender- matched healthy controls (collected at Beijing Hospital in March 2015) were treated with Cinaciguat for 8 hours. Then RNA of peripheral leukocytes was extracted and performed with reverse transcription and Real-time PCR to detect the mRNA level of PAI-2, which was compared between healthy controls and patients with pulmonary hypertension, before and after the treatment of Cinaciguat. At last, the correlation of PAI-2 mRNA level and the clinic severity of pulmonary hypertension were identified.

RESULTS: The mRNA and protein expression levels of PAI-2 were promoted by Cinaciguat in human pulmonary arterial smooth muscle cells. The baseline mRNA level of PAI-2 in peripheral leukocytes was significantly lower in PAH patients compared to the healthy controls (0.201±0.152, 0.660±0.440, P=0.021). There was no significant difference in the mRNA expression level of PAI-2 between the CTEPH patients and controls (0.428±0.364, 0.769±0.682, P=0.152). After Cinaciguat treatment, the mRNA expression levels of PAI-2 were up-regulated in PAH patients and CTEPH patients (1.352±1.127, 1.203±1.008), there was no significant difference in the mRNA expression level of PAI-2 among the PAH patients, CTEPH patients and controls (P=0.130, P=0.534). The baseline mRNA level of PAI-2 was negative correlated with echocardiography-estimated systolic pulmonary arterial pressure (sPAP) (r=-0.744, P=0.034).

CONCLUSIONS: The mRNA expression level of PAI-2 is significantly down-regulated in peripheral blood leucocytes and up-regulated by sGC activator in pulmonary hypertension. PAI-2 could be used as potential biomarker of pulmonary vascular remodeling in PAH.