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 language | English (US) |
|---|---|
| Article number | 0150480 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2016 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung
AU - Rafikova, Olga
AU - Meadows, Mary L.
AU - Kinchen, Jason M.
AU - Mohney, Robert P.
AU - Maltepe, Emin
AU - Desai, Ankit
AU - Yuan, Jason
AU - Garcia, Joe GN
AU - Fineman, Jeffrey R.
AU - Rafikov, Ruslan
AU - Black, Stephen M.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84961151290&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0150480
DO - 10.1371/journal.pone.0150480
M3 - Article
C2 - 26937637
AN - SCOPUS:84961151290
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - 0150480
ER -