De novo synthesize of bile acids in pulmonary arterial hypertension lung.
Although multiple, complex molecular studies have been done for understanding the development and progression of pulmonary hypertension (PAH), little is known about the metabolic heterogeneity of PAH. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we found bile acid metabolites, which are normally product derivatives of the liver and gallbladder, were highly increased in the PAH lung. Microarray showed that the gene encoding cytochrome P450 7B1 (CYP7B1), an isozyme for bile acid synthesis, was highly expressed in the PAH lung compared with the control. CYP7B1 protein was found to be primarily localized on pulmonary vascular endothelial cells suggesting de novo bile acid synthesis may be involved in the development of PAH. Here, by profiling the metabolomic heterogeneity of the PAH lung, we reveal a newly discovered pathogenesis mechanism of PAH.
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.|MaRS Centre, Toronto Medical Discovery Tower, 2nd Floor Rm 2-817, 101 College Street, Toronto, ON M5G 1L7 Canada.
Yidan D
YD
Zhao
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Hana Z H
HZH
Yun
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Jenny
J
Peng
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Li
L
Yin
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Lei
L
Chu
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Licun
L
Wu
Metabolon, Incorporated, 617 Davis Drive, Durham, NC 27713 USA.
Ryan
R
Michalek
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Mingyao
M
Liu
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Shaf
S
Keshavjee
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.
Thomas
T
Waddell
Clinical Studies Resource Centre, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON Canada.
John
J
Granton
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University of Toronto, Toronto, ON Canada.|MaRS Centre, Toronto Medical Discovery Tower, 2nd Floor Rm 2-817, 101 College Street, Toronto, ON M5G 1L7 Canada.
Marc
M
de Perrot
Bile acid pathway; Lung; Pulmonary arterial hypertension