Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Nagy, BM; Nagaraj, C; Meinitzer, A; Sharma, N; Papp, R; Foris, V; Ghanim, B; Kwapiszewska, G; Kovacs, G; Klepetko, W; Pieber, TR; Mangge, H; Olschewski, H; Olschewski, A.
Importance of kynurenine in pulmonary hypertension.
Am J Physiol Lung Cell Mol Physiol. 2017; 313(5):L741-L751
Doi: 10.1152/ajplung.00517.2016
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- Führende Autor*innen der Med Uni Graz
- Nagy Miklos Bence
- Olschewski Horst
- Co-Autor*innen der Med Uni Graz
- Chandran Nagaraj
- Foris Vasile
- Kovacs Gabor
- Kwapiszewska-Marsh Grazyna
- Mangge Harald
- Meinitzer Andreas
- Olschewski Andrea
- Papp Rita
- Pieber Thomas
- Sharma Neha
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- Abstract:
- The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hypertension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to investigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine, and kynurenic acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls, and 20 patients with chronic lung disease or metabolic syndrome without PH. Laser-dissected pulmonary arteries from IPAH and control lungs were tested for the expression of indoleamine-2, 3-dioxygenase (IDO), the rate-limiting enzyme for the conversion from tryptophan to kynurenine. Acute effects of kynurenine were tested in pulmonary vascular preparations, two different models of chronic pulmonary hypertension (PH), and in human pulmonary arterial smooth muscle cells (hPASMCs). In IPAH vs. control serum, kynurenine was significantly elevated (3.6 ± 0.2 vs. 2.6 ± 0.1 µM, P < 0.0001), and strongly associated with PH (area under the curve = 0.86), but kynurenine levels were not elevated in lung disease and metabolic syndrome. Among all investigated tryptophan metabolites, kynurenine displayed the strongest correlation with mean pulmonary arterial pressure (mPAP) (ρ: 0.770, P < 0.0001). Tryptophan was significantly decreased in IPAH lungs; however, IDO expression was not changed. In hPASMCs, kynurenine increased both cAMP and cGMP; in intrapulmonary arteries, it relaxed the preconstriction via NO/cGMP and cAMP pathways, and in two models of established PH, it acutely decreased the mPAP. Our data suggest that kynurenine elevation might be specifically associated with mPAP; kynurenine acts on hPASMCs in synergy with NO and exerts acute pulmonary vasodilatation in chronic PH models. Kynurenine might provide both a new biomarker and a new therapeutic option for PH. Copyright © 2017 the American Physiological Society.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Animals -
- Child -
- Chronic Disease -
- Female -
- Humans -
- Hypertension, Pulmonary - metabolism
- Hypertension, Pulmonary - pathology
- Kynurenine - metabolism
- Lung - metabolism
- Lung - physiopathology
- Male -
- Mice, Inbred C57BL -
- Middle Aged -
- Myocytes, Smooth Muscle - metabolism
- Pulmonary Artery - metabolism
- Pulmonary Artery - pathology
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- Young Adult -
- Find related publications in this database (Keywords)
- pulmonary hypertension
- circulating metabolite
- vasodilation
- kynurenine
- laser-capture microdissection