Expression and Correlation of Hypoxia-Inducible Factor-1α (HIF-1α) with Pulmonary Artery Remodeling and Right Ventricular Hypertrophy in Experimental Pulmonary Embolism.

ABSTRACT

BACKGROUND We investigated the expression of HIF-1α (hypoxia-inducible factor-1α) and its correlations with pulmonary artery remodeling and right ventricular hypertrophy in PE (pulmonary embolism) rats. MATERIAL AND METHODS After the PE rat model was established, the dynamic changes of mPAP (mean pulmonary artery pressure), PAMT (relative medial thickness of small pulmonary arteries), WA/TA (vessel wall area/total area), and RVHI (right ventricular hypertrophy index) were detected. Then, histomorphology of pulmonary vascular was observed, followed by HIF-1α mRNA and protein for pulmonary artery and right ventricle were checked via in situ hybridization and immunohistochemistry, respectively. The correlations between HIF-1α and mPAP, PAMT, WA/TA, and RVHI were analyzed. RESULTS The mPAP level increased from the initial time to 12 weeks of PE and reached the peak at 12 weeks. After 4 weeks of PE, PAMT increased compared with the initial control group (p<0.05), and increased further after 8 weeks and 12 weeks. Changes of the vessel WA/TA were the same as PAMT. Compared with the initial control group, RVHI increased at 8 weeks (p<0.05) and 12 weeks of PE (p<0.01). HIF-1α mRNA and protein were positively correlated with mPAP, PAMT, and WA/TA in pulmonary arteries. HIF-1α mRNA and protein were positively correlated with mPAP, PAMT, WA/TA, and RVHI in right ventricles (p<0.01). CONCLUSIONS HIF-1α mRNA and protein are expressed in the pulmonary artery and right ventricular of PE rats, and HIF-1α may correlate with pulmonary artery remodeling and right ventricular hypertrophy in rats with PE.