Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways
Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administrat...
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doaj-49c42f612639466f887aef965d28f33f2020-11-25T02:19:45ZengMDPI AGGenes2073-44252020-01-0111212610.3390/genes11020126genes11020126Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional PathwaysRajamma Mathew0Jing Huang1Sanda Iacobas2Dumitru A. Iacobas3Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USADepartment of Pediatrics, New York Medical College, Valhalla, NY 10595, USADepartment of Pathology, New York Medical College, Valhalla, NY 10595, USAPersonalized Genomics Laboratory, Center for Computational Systems Biology, Roy G Perry College of Engineering, Prairie View A&M University, Prairie View, TX 77446, USAPulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administration of monocrotaline (CM), or (3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations, as well as neointimal lesions and obliteration of the lumen in small arteries. We found that PH increased the expression of caveolin1, matrix metallopeptidase 2, and numerous inflammatory and cell proliferation genes. The cell cycle, vascular smooth muscle contraction, and oxidative phosphorylation pathways, as well as their interplay, were largely perturbed. Our results also suggest that the upregulated <i>Rhoa</i> (Ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed, especially in the HM group, indicate metabolic shift toward aerobic glycolysis.https://www.mdpi.com/2073-4425/11/2/126aerobic glycolysiscaveolin1hypoxiamonocrotalineoxidative phosphorylationrhoa |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rajamma Mathew Jing Huang Sanda Iacobas Dumitru A. Iacobas |
spellingShingle |
Rajamma Mathew Jing Huang Sanda Iacobas Dumitru A. Iacobas Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways Genes aerobic glycolysis caveolin1 hypoxia monocrotaline oxidative phosphorylation rhoa |
author_facet |
Rajamma Mathew Jing Huang Sanda Iacobas Dumitru A. Iacobas |
author_sort |
Rajamma Mathew |
title |
Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways |
title_short |
Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways |
title_full |
Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways |
title_fullStr |
Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways |
title_full_unstemmed |
Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways |
title_sort |
pulmonary hypertension remodels the genomic fabrics of major functional pathways |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2020-01-01 |
description |
Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administration of monocrotaline (CM), or (3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations, as well as neointimal lesions and obliteration of the lumen in small arteries. We found that PH increased the expression of caveolin1, matrix metallopeptidase 2, and numerous inflammatory and cell proliferation genes. The cell cycle, vascular smooth muscle contraction, and oxidative phosphorylation pathways, as well as their interplay, were largely perturbed. Our results also suggest that the upregulated <i>Rhoa</i> (Ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed, especially in the HM group, indicate metabolic shift toward aerobic glycolysis. |
topic |
aerobic glycolysis caveolin1 hypoxia monocrotaline oxidative phosphorylation rhoa |
url |
https://www.mdpi.com/2073-4425/11/2/126 |
work_keys_str_mv |
AT rajammamathew pulmonaryhypertensionremodelsthegenomicfabricsofmajorfunctionalpathways AT jinghuang pulmonaryhypertensionremodelsthegenomicfabricsofmajorfunctionalpathways AT sandaiacobas pulmonaryhypertensionremodelsthegenomicfabricsofmajorfunctionalpathways AT dumitruaiacobas pulmonaryhypertensionremodelsthegenomicfabricsofmajorfunctionalpathways |
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