@article{57dc1f6097074b1cb1b027a4d749bc00,
title = "Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung",
abstract = "There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH.",
author = "Olga Rafikova and Meadows, {Mary L.} and Kinchen, {Jason M.} and Mohney, {Robert P.} and Emin Maltepe and Desai, {Ankit A.} and Yuan, {Jason X.J.} and Garcia, {Joe G.N.} and Fineman, {Jeffrey R.} and Ruslan Rafikov and Black, {Stephen M.}",
note = "Funding Information: This research was supported in part by National Institutes of Health grants HL60190 (to SMB), HL67841 (to SMB), and P01HL0101902; by an Entelligence Actelion Young Investigator Award for Research Excellence in Pulmonary Hypertension and by F32HL103136 (to OR); a Scientist Development Grant (14SDG20480354) from the American Heart Association National Office (to RR). Metabolon inc. provided support in the form of salaries for authors JMK and RPM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ''author contributions'' section. This research was supported in part by National Institutes of Health grants HL60190 (to SMB), HL67841 (to SMB), and P01HL0101902; by an Entelligence Actelion Young Investigator Award for Research Excellence in Pulmonary Hypertension and by F32HL103136 (to OR); a Scientist Development Grant (14SDG20480354) from the American Heart Association National Office (to RR). Metabolon inc. provided support in the form of salaries for authors JMK and RPM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
year = "2016",
month = mar,
doi = "10.1371/journal.pone.0150480",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",
}