Expression and analyses of the HIF-1 pathway in the lungs of humans with pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is characterized by endothelial dysfunction and structural remodeling of the pulmonary vasculature, mediated initially by reduced oxygen availability in the lungs. Hypoxia inducible factor (HIF), consisting of the functional subunit, HIF‑1α, and the constitutively expressed HIF‑1β, is involved in the pathological processes associated with hypoxia. In the current study, the sequences of cDNAs and amino acids of HIF were characterized and analyzed using online bioinformatics tools. To further evaluate whether HIF accounts for the occurrence of PAH, the present study determine the expression and phosphorylation levels of HIF and its associated pathways, including extracellular signal‑regulated kinase (Erk)1/2 and phosphoinositide 3‑kinase (PI3K)/Akt, in the lungs of patients with PAH by reverse transcription‑quantitative polymerase chain reaction and western blotting. The mRNA expression levels of PI3K, Erk2, and HIF‑1α in the patients with PAH were significantly higher, compared with those in the control group, by 3.6‑fold (P<0.01), 4.06‑fold and 2.64‑fold (P<0.05), respectively. No significant differences were found in the mRNA and protein levels of Akt between the two groups (P>0.05). The protein levels of phosphorylated (p‑)Akt, Erk1/2, p‑Erk1/2, HIF‑1α and HIF‑1β were significantly increased by 5.89‑, 0.5‑, 0.59‑, 1.46‑ and 0.92‑fold, respectively, in the patients with PAH, compared with those in the controls group (P<0.01 for p‑Akt, Erk1/2; P<0.05 for p‑Erk1/2, HIF‑1α and HIF‑1β). These findings suggested that the mitogen‑activated protein kinase and PI3K/Akt signaling pathways, and HIF‑1 may perform a specific function in the pathogenesis of PAH.
Laboratory of Cardiovascular Diseases, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Wei
W
Lei
Laboratory of Cardiovascular Diseases, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Yuan
Y
He
Laboratory of Vascular Surgery, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Xiaorong
X
Shui
Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Guoming
G
Li
Laboratory of Cardiovascular Diseases, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Guosen
G
Yan
Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Yu
Y
Zhang
Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Shian
S
Huang
Laboratory of Cardiovascular Diseases, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Can
C
Chen
Institute of Medical Systems Biology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
Yuanlin
Y
Ding
D000293:Adolescent; D000328:Adult; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics
C497396:ARNT protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1