{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:46:27Z","timestamp":1790041587325,"version":"4.0.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870288"],"award-info":[{"award-number":["81870288"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"crossref","award":["2019XK310001 & 2018TX31002"],"award-info":[{"award-number":["2019XK310001 & 2018TX31002"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY15H020008"],"award-info":[{"award-number":["LY15H020008"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianjin Science and Technology Commission","award":["18PTZWHZ00060"],"award-info":[{"award-number":["18PTZWHZ00060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:p>\n                    The molecular mechanisms underlying pulmonary arterial hypertension (PAH) in congenital ventricular septal defects (VSD) are unclear. We aimed to reveal molecular pathways and potential biomarkers by multi-omics analysis in VSD-PAH. Plasma from 160 children, including 120 VSD patients with\/without PAH and 40 healthy children was studied by integrated proteomics, metabolomics, and bioinformatics analyses. Proteomics identified 107 differential proteins (DPs) between patients with\/without PAH including significantly increased adiponectin (ADIPO), dopamine \u03b2-hydroxylase (DBH), alanyl membrane aminopeptidase (ANPEP), transferrin receptor 1, and glycoprotein Ib platelet \u03b1-subunit and decreased guanine nucleotide-binding protein Gs in VSD-PAH. Metabolomics discovered 191 differential metabolites between patients with\/without PAH, including elevation of serotonin, taurine, creatine, sarcosine, and 2-oxobutanoate, and decrease of vanillylmandelic acid, 3,4-dihydroxymandelate, 15-keto-prostaglandin F\n                    <jats:sub>2\u03b1,<\/jats:sub>\n                    fructose 6-phosphate, l-glutamine, dehydroascorbate, hydroxypyruvate, threonine, l-cystine, and 1-aminocyclopropane-1-carboxylate. The DPs were validated in a new cohort of patients ( n = 80). Integrated analyses identified key pathways, including cAMP, ECM receptor interaction, AMPK, hypoxia-inducible factor 1, PI3K-Akt signaling pathways, and amino acid metabolisms. Increased plasma protein levels of DBH, ADIPO, and ANPEP were found to be independently associated with the occurrence of PAH, with a new total risk score from these three proteins developed for clinical diagnosis. In this integrated multi-omics analysis in VSD-PAH patients, we have, for the first time, found that VSD-PAH patients present important differential proteins, metabolites, and key pathways. We have developed a total risk score (based on the plasma concentration of DBH, ANPEP, and ADIPO) as a predictor of development of PAH in CHD-VSD patients. Therefore, these proteins may be used as biomarkers, and the new total risk score has significant clinical implications in the diagnosis of PAH.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00167.2020","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T12:39:40Z","timestamp":1599050380000},"page":"L810-L822","source":"Crossref","is-referenced-by-count":25,"title":["Protein biomarkers and risk scores in pulmonary arterial hypertension associated with ventricular septal defect: integration of multi-omics and validation"],"prefix":"10.1152","volume":"319","author":[{"given":"Chao","family":"Yuan","sequence":"first","affiliation":[{"name":"Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences, Tianjin, China"},{"name":"School of Medicine, Nankai University, Tianjin, 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