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 A. Desai, Jason X.J. Yuan, Joe G.N. Garcia, Jeffrey R. Fineman, Ruslan Rafikov, Stephen Matthew Black

Research output: Contribution to journalArticle

11 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

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

Cite this

Rafikova, O., Meadows, M. L., Kinchen, J. M., Mohney, R. P., Maltepe, E., Desai, A. 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 A.; Yuan, Jason X.J.; Garcia, Joe G.N.; Fineman, Jeffrey R.; Rafikov, Ruslan; Black, Stephen Matthew.

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, AA, Yuan, JXJ, 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 O, Meadows ML, Kinchen JM, Mohney RP, Maltepe E, Desai AA et al. Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung. PloS one. 2016 Mar 1;11(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 A. ; Yuan, Jason X.J. ; Garcia, Joe G.N. ; Fineman, Jeffrey R. ; Rafikov, Ruslan ; Black, Stephen Matthew. / 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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