BackgroundHypoxic pulmonary hypertension (HPH) is a syndrome of abnormally elevated pulmonary artery pressure, and it is mostly caused by vasoconstriction and remodeling of the pulmonary artery induced by long-term chronic hypoxia. There is a high incidence of HPH, a short survival time of the patients, but currently no effective treatments.MethodsIn this study, HPH-related single cell sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data were downloaded from the public database of Gene Expression Omnibus (GEO) for bioinformatics analysis in order to find out genes with important regulatory roles in the development of HPH. 523 key genes were identified through cell subpopulation identification and trajectory analysis of the downloaded scRNA-seq data, and 41 key genes were identified through weighted correlation network analysis (WGCNA) of the bulk RNA-seq data. Three key genes: Hpgd, Npr3 and Fbln2 were identified by taking intersection of the key genes obtained above, and Hpgd was finally selected for subsequent verification. The human pulmonary artery endothelial cells (hPAECs) were treated with hypoxia for different periods of time, and it was found that the expression of Hpgd decreased in hypoxia-treated hPAECs in a time-dependent manner. In order to further confirm whether Hpgd affects the occurrence and development of HPH, Hpgd was overexpressed in hPAECs.ResultsHpgd was confirmed to regulate the proliferation activity, apoptosis level, adhesiveness and angiogenesis ability of hypoxia-treated hPAECs through multiple experiments.ConclusionsDownregulation of Hpgd can improve the proliferation activity, reduce apoptosis, and enhance adhesion and angiogenesis in endothelial cells (ECs), thus promoting the occurrence and development of HPH.
机构:
Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USAHarvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA
Leopold, Jane A.
Maron, Bradley A.
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h-index: 0
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Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA
Vet Affairs Boston Healthcare Syst, Div Cardiol, Boston, MA 02132 USAHarvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA
机构:
Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Braga, Cassia Lisboa
Felix, Nathane Santanna
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Felix, Nathane Santanna
Teixeira, Douglas Esteves
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机构:
Univ Fed Rio de Janeiro, Lab Biochem & Cell Signaling, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Teixeira, Douglas Esteves
Vieira, Juliana Borges
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Vieira, Juliana Borges
Silva-Aguiar, Rodrigo Pacheco
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机构:
Univ Fed Rio de Janeiro, Lab Biochem & Cell Signaling, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Silva-Aguiar, Rodrigo Pacheco
Bose, Rebecca Madureira
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Bose, Rebecca Madureira
Antunes, Mariana Alves
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Antunes, Mariana Alves
Rocha, Nazareth de Novaes
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Lab Pulm Invest, Rio De Janeiro, Brazil
Fluminense Fed Univ, Niteroi, RJ, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Rocha, Nazareth de Novaes
Caruso-Neves, Celso
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Univ Fed Rio de Janeiro, Lab Biochem & Cell Signaling, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Caruso-Neves, Celso
Cruz, Fernanda Ferreira
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Cruz, Fernanda Ferreira
Macedo Rocco, Patricia Rieken
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
Macedo Rocco, Patricia Rieken
Silva, Pedro Leme
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Lab Pulm Invest, Rio De Janeiro, BrazilLab Pulm Invest, Rio De Janeiro, Brazil
机构:
Fourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R ChinaFourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R China
Ma, Hongwei
Xu, Dunquan
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h-index: 0
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Fourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R ChinaFourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R China
Xu, Dunquan
Wu, Yaqiong
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h-index: 0
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Shaanxi Normal Univ, Sch Life Sci, Xian, Peoples R ChinaFourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R China
Wu, Yaqiong
Ma, Yongtao
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Kaifeng Childrens Hosp, Pediat Intense Care Unit, Xian, Peoples R ChinaFourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R China
Ma, Yongtao
Li, Zhichao
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Fourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R ChinaFourth Mil Med Univ, Dept Pathol & Pathophysiol, 169 Changlexi Rd, Xian 710032, Peoples R China
Li, Zhichao
JOURNAL OF MEDICAL HYPOTHESES AND IDEAS,
2015,
9
(01):
: 29
-
37
机构:
Univ Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Irwin, David C.
Baek, Jin Hyen
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Lab Biochem & Vasc Biol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Baek, Jin Hyen
Hassell, Kathryn
论文数: 0引用数: 0
h-index: 0
机构:
Colorado Sickle Cell Treatment & Res Ctr, Aurora, CO 80045 USA
Univ Colorado Denver, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Hassell, Kathryn
Nuss, Rachelle
论文数: 0引用数: 0
h-index: 0
机构:
Colorado Sickle Cell Treatment & Res Ctr, Aurora, CO 80045 USA
Univ Colorado Denver, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Nuss, Rachelle
Eigenberger, Paul
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Eigenberger, Paul
Lisk, Christina
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h-index: 0
机构:
Univ Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Lisk, Christina
Loomis, Zoe
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h-index: 0
机构:
Colorado Sickle Cell Treatment & Res Ctr, Aurora, CO 80045 USA
Univ Colorado Denver, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Loomis, Zoe
Maltzahn, Joanne
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h-index: 0
机构:
Univ Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Maltzahn, Joanne
Stenmark, Kurt R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado Denver, Sch Med, Cardiovasc Pulm Res Grp, Pediat, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Stenmark, Kurt R.
Nozik-Grayck, Eva
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado Denver, Sch Med, Cardiovasc Pulm Res Grp, Pediat, Aurora, CO 80045 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
Nozik-Grayck, Eva
Buehler, Paul W.
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h-index: 0
机构:
Univ Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
US FDA, Lab Biochem & Vasc Biol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USAUniv Colorado Denver, Sch Med, Div Cardiol, Cardiovasc Pulm Res Grp, Aurora, CO 80045 USA
机构:
Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Lemay, Sarah-Eve
Grobs, Yann
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机构:
Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Grobs, Yann
Romanet, Charlotte
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Romanet, Charlotte
Martineau, Sandra
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Martineau, Sandra
Salem, Mabrouka
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Salem, Mabrouka
Shimauchi, Tsukasa
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Shimauchi, Tsukasa
Breuils-Bonnet, Sandra
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Breuils-Bonnet, Sandra
Bourgeois, Alice
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h-index: 0
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Bourgeois, Alice
Theberge, Charlie
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Theberge, Charlie
Pelletier, Andreanne
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Pelletier, Andreanne
Potus, Francois
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Potus, Francois
Provencher, Steeve
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Laval Univ, Dept Med, Quebec City, PQ, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Provencher, Steeve
Bonnet, Sebastien
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Laval Univ, Dept Med, Quebec City, PQ, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Bonnet, Sebastien
Boucherat, Olivier
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Quebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada
Laval Univ, Dept Med, Quebec City, PQ, CanadaQuebec Heart & Lung Inst Res Ctr, Pulm Hypertens Res Grp, 2725 Chemin St Foy, Quebec City, PQ G1V 4G5, Canada