• Qi-fang Li and Ai-guo Dai.
• Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China.
• Zhonghua Jie He He Hu Xi Za Zhi. 2006 Feb 1; 29 (2): 113-7.

ObjectiveTo differentiate the expression patterns of all hypoxia-inducible factor alpha (HIF-alpha) subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha) in pulmonary artery of rats undergoing systemic hypoxia.MethodsForty male healthy wistar rats were assigned randomly to 5 groups, 8 rats per group, then exposed to hypoxia [O2, (10.0 +/- 0.5)%] for 0 d (H(0)), 3 d (H(3)), 7 d (H(7)), 14 d (H(14)) and 21 d (H(21)) respectively, 8 h per day intermittently. Mean pulmonary arterial pressure (mPAP), arterial wall area (WA, microm), pulmonary artery medium thickness (PAMT%) and right ventricle hypertrophy index (RVHI) were measured. HIF-1alpha, HIF-2alpha and HIF-3alpha gene expression were determined by immunohistochemistry, in situ hybridization and Western blot.ResultsmPAPs in H(7), H(0) and H(14) groups were [(18.40 +/- 0.40) mm Hg, 1 mm Hg = 0.133 kPa], [(14.40 +/- 0.40) mm Hg] and [(21.20 +/- 0.20) mm Hg], respectively, statistically different when H(7) group was compared with H(0) and H(14) groups (all P < 0.05). Arterial morphology showed that WA%, PAMT and RVHI% in H(7) group were (47.8 +/- 0.8)%, (12.3 +/- 0.5) microm, (24.0 +/- 1.0)%, respectively; in H(0) group were (35.5 +/- 1.3)%, (11.9 +/- 0.6)%, (23.6 +/- 0.5) microm, respectively; in H(21) group were (65.0 +/- 0.7)%, (23.0 +/- 0.8) microm, (27.7 +/- 1.0)%, respectively. When H(7) group was compared with H(0) group, only WA% was statistically different; when H(14) group was compared with H(0) group, all the three parameters were statistically different (P < 0.05). In situ hybridization demonstrated that the mRNA levels (absorbance, A) of HIF-1alpha, HIF-2alpha, and HIF-3alpha in H(14) group were 0.200 +/- 0.020, 0.080 +/- 0.010, 0.170 +/- 0.010, respectively; in H(7) group were 0.050 +/- 0.020, 0.160 +/- 0.020, 0.160 +/- 0.020, respectively; in H(0) group were 0.050 +/- 0.010, 0.140 +/- 0.020, 0.060 +/- 0.010, respectively. When H(7) group was compared with H(0) group, only HIF-3alpha was statistically different; when H(14) group was compared with H(0) group, all the three genes were significantly different (P < 0.05). Immunohistochemistry showed that HIF-1alpha, HIF-2alpha and HIF-3alpha protein levels in H(3) group were 0.200 +/- 0.020, 0.020 +/- 0.010, 0.050 +/- 0.010, respectively; in H(14) group were 0.160 +/- 0.010, 0.100 +/- 0.020, 0.160 +/- 0.010, respectively; in H(7) group were 0.220 +/- 0.020, 0.030 +/- 0.010, 0.180 +/- 0.020, respectively; in H(0) group were 0.050 +/- 0.010, 0.020 +/- 0.010, 0.040 +/- 0.010, respectively. HIF-1alpha in H(3) group, HIF-2alpha in H(14) group, HIF-3alpha in H(7) and H(3) group were statistically different with that of H(0) group (P < 0.05). Protein bands of HIF-alpha subunits in lung tissue, measured by Western blot, showed that HIF-3alpha decreased in H(7) group as compared to H(0) group, but the other two proteins showed a marked increase in H(3) group as compared to H(0) group, and increased further corresponding to the duration of hypoxia and peaked in H(14) group as compared to H(7) group.ConclusionThe differential expression of the three HIF-alpha subunits may play a role in the development of hypoxia-induced pulmonary hypertension.

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