Coupling Factor 6 Is Upregulated in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Pulmonary arterial hypertension (PAH) is a rare and fatal disease. The prostacyclin (PGI₂) pathway is a well-known therapeutic target for PAH. As a novel vasoconstrictive peptide, coupling factor 6 (CF6) has been recognized as the only endogenous inhibitor of PGI₂. However, the relationship between CF6 and PAH is still unknown. In this study, we investigated the involvement of CF6 in PAH in rats.

A total of 80 Sprague-Dawley rats were randomly divided into 2 groups: a control group (with saline intraperitoneally) and a monocrotaline (MCT)-treated group (with MCT 60mg/kg intraperitoneal injection). The expression level of CF6 was measured by immunohistochemistry, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay. The plasma level of 6-keto-PGF_1α, a stable metabolite of PGI₂, was measured by enzyme-linked immunosorbent assay.

After MCT injection, although the plasma level of CF6 was markedly increased in a time-dependent manner, the level of 6-keto-PGF_1α was decreased in the MCT rats as compared to that in the controls (P < 0.05). Reverse transcription polymerase chain reaction indicated that the lung tissue level of CF6 messenger RNA (mRNA) in the MCT rats was significantly upregulated compared to the level in the controls. There was an intense CF6 immunostain concentrated on the lung tissue of the MCT rats compared with the controls. Univariate analysis indicated that the plasma level of CF6 was not correlated with blood pressure, fasting blood glucose, cholesterol (high-density lipoprotein, triglycerides and total cholesterol) or C-reactive protein level.

These results demonstrated that CF6 was elevated in MCT-induced PAH rats and may play an important role in the development of PAH.