Altered Hypoxic-Adenosine Axis and Metabolism in Group III Pulmonary Hypertension.

Autor:	Garcia-Morales LJ; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas.; 2 Methodist DeBakey Heart and Vascular Center, and Methodist J. C. Walter Jr. Transplant Center, the Methodist Hospital, Houston, Texas., Chen NY; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Weng T; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Luo F; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Davies J; 3 Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Philip K; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Volcik KA; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Melicoff E; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Amione-Guerra J; 2 Methodist DeBakey Heart and Vascular Center, and Methodist J. C. Walter Jr. Transplant Center, the Methodist Hospital, Houston, Texas., Bunge RR; 2 Methodist DeBakey Heart and Vascular Center, and Methodist J. C. Walter Jr. Transplant Center, the Methodist Hospital, Houston, Texas., Bruckner BA; 2 Methodist DeBakey Heart and Vascular Center, and Methodist J. C. Walter Jr. Transplant Center, the Methodist Hospital, Houston, Texas., Loebe M; 2 Methodist DeBakey Heart and Vascular Center, and Methodist J. C. Walter Jr. Transplant Center, the Methodist Hospital, Houston, Texas., Eltzschig HK; 4 Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado; and., Pandit LM; 5 Department of Internal Medicine, Baylor College of Medicine, Houston, Texas., Blackburn MR; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas., Karmouty-Quintana H; 1 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas.
Jazyk:	angličtina
Zdroj:	American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2016 Apr; Vol. 54 (4), pp. 574-83.
DOI:	10.1165/rcmb.2015-0145OC
Abstrakt:	Group III pulmonary hypertension (PH) is a highly prevalent and deadly lung disorder with limited treatment options other than transplantation. Group III PH affects patients with ongoing chronic lung injury, such as idiopathic pulmonary fibrosis (IPF). Between 30 and 40% of patients with IPF are diagnosed with PH. The diagnosis of PH has devastating consequences to these patients, leading to increased morbidity and mortality, yet the molecular mechanisms involved in the development of PH in patients with chronic lung disease remain elusive. Our hypothesis was that the hypoxic-adenosinergic system is enhanced in patients with group III PH compared with patients with IPF with no PH. Explanted lung tissue was analyzed for markers of the hypoxic-adenosine axis, including expression levels of hypoxia-inducible factor (HIF)-1A, adenosine A2B receptor, CD73, and equilibrative nucleotide transporter-1. In addition, we assessed whether altered mitochondrial metabolism was present in these samples. Increased expression of HIF-1A was observed in tissues from patients with group III PH. These changes were consistent with increased evidence of adenosine accumulation in group III PH. A novel observation of our study was of evidence suggesting altered mitochondrial metabolism in lung tissue from group III PH leading to increased succinate levels that are able to further stabilize HIF-1A. Our data demonstrate that the hypoxic-adenosine axis is up-regulated in group III PH and that subsequent succinate accumulation may play a part in the development of group III PH.
Databáze:	MEDLINE
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