Extracellular matrix dynamics in a rat model of pulmonary arterial hypertension: unveiling the role of hyaluronan in disease pathology

Objective: We aimed to investigate the feasibility of conducting extracellular matrix studies within this rat model. Materials and methods: This study involved 24 Sprague Dawley rats, divided into two groups. Group 1 served as the normoxia control, while Group 2 is SU-5416 pulmonary arterial hypertension (PAH) model. Pulmonary artery pressure (PAP) was measured in both groups using a micro-catheter Power Lab device. Hyaluronan (HA) plasma level was quantified through ELISA, and HA levels were determined via lung tissue immunostaining. Western blotting detected protein levels, and real-time RT-PCR assessed mRNA expressions for HAS1, HAS2, and HAS3 and hyal1 and hyal2. Results: HA plasma levels were markedly higher in PAH rats compared to controls (HA ng/ml, mean +/- SD: PAH 3.8 +/- 0.41, control 1.96 +/- 0.31, P < 0.0015). Protein analysis showed no detection of HAS1 and HAS3 proteins in both groups, while HAS2 protein expression was notably higher in PAH rats than controls (HAS2 levels, mean +/- SD: PAH 2.0 +/- 0.5, control 0.86 +/- 0.07, P = 0.0493). Hyal2 protein expression remained consistent between groups (Hyal2 levels, mean +/- SD: PAH 1.41 +/- 0.18, control 1.05 +/- 0.14, P = 0.214). No mRNA expression of HAS1, HAS3, and Hyal1 were detected in both groups, Hyal2 expression was identified in both without differences. HAS2 mRNA expression was present in both groups, with a significantly higher increase observed in the hypoxia SU-5416 PAH rat model compared to controls. Conclusion: Establishing an extracellular matrix profile in the rat model, resembling human PAH under hypoxia SU-5416 conditions, highlights the model's suitability for matrix studies.