Several human diseases have been associated with mitochondria! voltage-dependent anion channel-1 (VDAC1) due to its role in calcium ion transportation and apoptosis. Recent studies suggest that VDAC1 may interact with endothelium-dependent nitric oxide synthase (eNOS). Decreased VDAC1 expression may limit the physical interaction between VDAC1 and eNOS and thus impair nitric oxide production, leading to cardiovascular diseases, including pulmonary arterial hypertension (PAH). In this report, we conducted meta-analysis of genome-wide expression data to identify VDAC1 influenced genes implicated in PAH pathobiology. First, we identified the genes differentially expressed between wild-type and Vdac1 knockout mouse embryonic fibroblasts in hypoxic conditions. These genes were deemed to be influenced by VDAC1 deficiency. Gene ontology analysis indicates that the VDAC1 influenced genes are significantly associated with PAH pathobiology. Second, a molecular signature derived from the VDAC1 influenced genes was developed. We suggest that, VDAC1 has a protective role in PAH and the gene expression signature of VDAC1 influenced genes can be used to i) predict severity of pulmonary hypertension secondary to pulmonary diseases, ii) differentiate idiopathic pulmonary artery hypertension (IPAH) patients from controls, and iii) differentiate IPAH from connective tissue disease associated PAH.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/624396 |
| Date | January 2017 |
| Creators | Zhou, Tong, Tang, Haiyang, Han, Ying, Fraidenburg, Dustin, Kim, Young-Won, Lee, Donghee, Choi, Jeongyoon, Bang, Hyoweon, Ko, Jae-Hong |
| Contributors | Univ Arizona, Dept Med, Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA., Department of Medicine, University of Arizona, Tucson, AZ 85721, USA., Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China., Section of Pulmonary, Critical Care, Sleep & Allergy, Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612, USA., Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea., Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea., Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea., Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea., Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea. |
| Publisher | KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | Copyright © 2017 The Korean Physiological Society and The Korean Society of Pharmacology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License. |
| Relation | https://synapse.koreamed.org/DOIx.php?id=10.4196/kjpp.2017.21.3.353 |
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