Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.

TitleMetabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.
Publication TypeJournal Article
Year of Publication2016
AuthorsRafikova O, Meadows ML, Kinchen JM, Mohney RP, Maltepe E, Desai AA, Yuan JX-J, Garcia JGN, Fineman JR, Rafikov R, Black SM
JournalPLoS One
Volume11
Issue3
Paginatione0150480
Date Published2016
ISSN Number1932-6203
KeywordsAnimals, Blood Pressure, Carnitine, Disease Models, Animal, Disease Progression, Glutathione, Humans, Hypertension, Pulmonary, Hypertrophy, Right Ventricular, Lung, Male, Metabolic Networks and Pathways, Metabolome, Monocrotaline, Pulmonary Artery, Rats, Rats, Sprague-Dawley, Time Factors
Abstract

<p>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.</p>

DOI10.1371/journal.pone.0150480
Alternate JournalPLoS ONE
PubMed ID26937637
PubMed Central IDPMC4777490
Grant ListF32 HL103136 / HL / NHLBI NIH HHS / United States
P01HL0101902 / HL / NHLBI NIH HHS / United States
P01 HL101902 / HL / NHLBI NIH HHS / United States
HL67841 / HL / NHLBI NIH HHS / United States
F32HL103136 / HL / NHLBI NIH HHS / United States
R01 HL067841 / HL / NHLBI NIH HHS / United States
HL60190 / HL / NHLBI NIH HHS / United States
R01 HL060190 / HL / NHLBI NIH HHS / United States