Human PAH is characterized by a pattern of lipid-related insulin resistance

摘要: BACKGROUND. Pulmonary arterial hypertension (PAH) is a deadly disease of the small pulmonary vasculature with an increased prevalence insulin resistance (IR). Insulin regulates both glucose and lipid homeostasis. We sought to quantify glucose- lipid-related IR in human PAH, testing hypothesis that lipoprotein indices are more sensitive PAH. METHODS. Oral tolerance PAH patients triglyceride-matched (TG-matched) controls proteomic, metabolomics, analyses were performed controls. Results validated external cohort explanted lungs. RESULTS. similarly intolerant or by homeostasis metrics compared control when matched for metabolic syndrome. Using insulin-sensitive index, TG/HDL ratio, commonly than Proteomic metabolomic analysis demonstrated separation between controls, driven differences species. observed significant increase long-chain acylcarnitines, phosphatidylcholines, metabolism–related proteins, oxidized LDL receptor 1 (OLR1) plasma discovery validation cohort. had higher axis–related lipoprotein-based inflammation scores patient lung tissue showed enhanced OLR1 immunostaining within plexiform lesions accumulation macrophages. CONCLUSIONS. characterized alterations axes, manifest elevated circulating medium- acylcarnitines lipoproteins. Oxidized its may play role proinflammatory phenotype PAH. FUNDING. NIH {"type":"entrez-nucleotide","attrs":{"text":"DK096994","term_id":"187460004"}}DK096994, {"type":"entrez-nucleotide","attrs":{"text":"HL060906","term_id":"1051598402"}}HL060906, UL1 RR024975-01, TR000445-06, {"type":"entrez-nucleotide","attrs":{"text":"DK020593","term_id":"187398843"}}DK020593, P01 HL108800-01A1, TR002243; American Heart Association 13FTF16070002.