Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung

Olga Rafikova, Mary L. Meadows, Jason M. Kinchen, Robert P. Mohney, Emin Maltepe, Ankit Desai, Jason Yuan, Joe GN Garcia, Jeffrey R. Fineman, Ruslan Rafikov, Stephen M. Black

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article number0150480
JournalPLoS One
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

monocrotaline
Monocrotaline
Pulmonary Hypertension
hypertension
Rats
lungs
Lung
rats
Carnitine
Biosynthesis
Endothelial cells
Cell proliferation
Biomarkers
Glutathione
Animals
Metabolome
Glycolysis
carnitine
pulmonary artery
metabolomics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Rafikova, O., Meadows, M. L., Kinchen, J. M., Mohney, R. P., Maltepe, E., Desai, A., ... Black, S. M. (2016). Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung. PLoS One, 11(3), [0150480]. https://doi.org/10.1371/journal.pone.0150480

Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung. / Rafikova, Olga; Meadows, Mary L.; Kinchen, Jason M.; Mohney, Robert P.; Maltepe, Emin; Desai, Ankit; Yuan, Jason; Garcia, Joe GN; Fineman, Jeffrey R.; Rafikov, Ruslan; Black, Stephen M.

In: PLoS One, Vol. 11, No. 3, 0150480, 01.03.2016.

Research output: Contribution to journalArticle

Rafikova, O, Meadows, ML, Kinchen, JM, Mohney, RP, Maltepe, E, Desai, A, Yuan, J, Garcia, JGN, Fineman, JR, Rafikov, R & Black, SM 2016, 'Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung', PLoS One, vol. 11, no. 3, 0150480. https://doi.org/10.1371/journal.pone.0150480
Rafikova, Olga ; Meadows, Mary L. ; Kinchen, Jason M. ; Mohney, Robert P. ; Maltepe, Emin ; Desai, Ankit ; Yuan, Jason ; Garcia, Joe GN ; Fineman, Jeffrey R. ; Rafikov, Ruslan ; Black, Stephen M. / Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung. In: PLoS One. 2016 ; Vol. 11, No. 3.
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