Dataset Information

Metabolomic heterogeneity of severe pulmonary arterial hypertension

ABSTRACT: Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53408 | GEO | 2014/11/14

SECONDARY ACCESSION(S): PRJNA231932

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Dysfunction of pulmonary arterial endothelial cells (PAECs) is associated with the development and progression of vascular pathology. However, it remains unknown how pulmonary hypertension (PH) affects cellular composition and transcriptomic profile of pulmonary endothelium. Here, we have undertaken a single-cell, compartment specific approach to characterise alterations in PAECs associated with two different types of PH, i.e., pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with pulmonary fibrosis (PHPF). Our unbiased analysis showed that endothelium of medium / small caliber pulmonary arteries is composed of three subsets of endothelial cells (ECs). The analysis of healthy and PH endothelium revealed that the three populations are persistently represented in remodelled arteries. Additionally, an exploratory analysis of human aorta (AO) and coronary arteries (CA) endothelium revealed that, although similar gene expression patterns were noticeable, PAECs subpopulations proportions differs significantly from pulmonary arteries (PA) endothelium. To address whether EC heterogeneity is a prime feature of human endothelium, we also performed a similar analysis in a murine model of hypoxia, revealing that similar EC populations were evident in this animal model. Comparative analysis of EC subpopulations in healthy and PH EC identified a common genetic deregulation accompanying vascular remodelling. Even though murine EC displayed some similarities with human EC subpopulations, the intense re-programming associated with hypoxia associated vascular remodelling displayed significant differences compared to the human disease. Finally, in depth comparative analysis of PAH and PHPF EC highlighted the development of disease-specific transcriptomic alterations in the three populations. Therefore, characterisation of transcriptomic differences in the endothelial bed of PAH and PHPF patients can facilitate identification of novel, disease-specific therapeutic targets.

Dataset Information

Metabolomic heterogeneity of severe pulmonary arterial hypertension

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets