Preprint Article Version 1 This version is not peer-reviewed

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Version 1 : Received: 19 December 2019 / Approved: 21 December 2019 / Online: 21 December 2019 (10:48:00 CET)

A peer-reviewed article of this Preprint also exists.

Mathew, R.; Huang, J.; Iacobas, S.; Iacobas , D.A. Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways. Genes 2020, 11, 126. Mathew, R.; Huang, J.; Iacobas, S.; Iacobas , D.A. Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways. Genes 2020, 11, 126.

Journal reference: Genes 2020, 11, 126
DOI: 10.3390/genes11020126

Abstract

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 weeks 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 and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (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 HM group, indicate metabolic shift towards aerobic glycolysis.

Subject Areas

aerobic glycolysis; caveolin1; hypoxia; monocrotaline; oxidative phosphorylation; RhoA

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