Aberrant Long-Chain Fatty Acid Metabolism Associated with Evolving Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Am J Physiol Lung Cell Mol Physiol. 2024 Apr 23. doi: 10.1152/ajplung.00057.2024. Online ahead of print.ABSTRACTWe sought to investigate differential metabolism in patients with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) versus those who do not, as a method of identifying potential disease biomarkers. In a nested case-control design, serum metabolites were assayed in SSc subjects who developed right heart catheterization-confirmed PAH (n=22) while under surveillance in a longitudinal cohort from Johns Hopkins, then compared to metabolites assayed in matched SSc patients who did not develop PAH (n=22). Serum samples were collected at "proximate" (within 12 months) and "distant" (within 1-5 years) time points relative to PAH diagnosis. Metabolites were identified using liquid chromatography-mass spectroscopy (LC-MS). An LC-MS dataset from SSc subjects with either mildly elevated pulmonary pressures or overt PAH from the University of Michigan was compared. Differentially abundant metabolites were tested as predictors of PAH in two additional validation SSc cohorts. Long-chain fatty acid metabolism (LCFA) consistently differed in SSc-PAH versus SSc without PH. LCFA metabolites discriminated SSc-PAH patients with mildly elevated pressures in the Michigan cohort and predicted SSc-PAH up to two years prior to clinical diagnosis in the Hopkins cohort. Acylcholines containing LCFA residues and linoleic acid metabolites were most important for discrimin...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research