{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:52:40Z","timestamp":1785909160017,"version":"3.56.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to characterize serum metabolic profiles in hypertensive patients and investigate the regulatory role of tryptophan metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an integrated metabolomics strategy that combined non-targeted screening with targeted validation. From November 2022 to November 2023, we enrolled 25 newly diagnosed, treatment-na\u00efve hypertensive patients and 25 age- and sex-matched healthy controls (1:1 ratio) from a local Shanghai hospital, together with their clinical baseline data. Non-targeted metabolomics, combined with Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were used to identify differential metabolic pathways. Subsequent targeted metabolomics analysis was conducted to quantify key molecules involved in the tryptophan metabolic pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Non-targeted metabolomics revealed 2,931 metabolites, with 759 showing differential expression (296 up-regulated and 463 down-regulated), emphasizing tryptophan metabolism as the central dysfunctional pathway. Targeted validation confirmed abnormalities in three branches of tryptophan metabolism: 5-hydroxytryptamine (5-HT) was down-regulated by 30% (Fold change\u2009=\u20090.69,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002), while five metabolites, such as 5-HT acid (Fold change\u2009=\u20091.33,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002) and kynurenine (Fold change\u2009=\u20091.35,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.004), exhibited significant up-regulation (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). Network pharmacology analysis indicated strong binding affinities between tryptamine metabolites (Serotonin and L-5-Hydroxytryptophan), kynurenine metabolites (3-Hydroxykynurenine and Kynurenine), and indole metabolites (Hydroxyindoleacetic acid and Indolelactic acid) with their respective targets SLC6A4, KYNU, and SLC6A2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dysregulation of the tryptophan metabolic network-characterized by kynurenine pathway activation, 5-HT pathway inhibition, and microbial-indole pathway imbalance-is a key pathological mechanism in hypertension. These key molecules regulate targets such as SLC6A4, KYNU, and SLC6A2, potentially offering mechanistic insights for future precision intervention studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1805381","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:41:11Z","timestamp":1785908471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated non-targeted and targeted metabolomics reveals tryptophan metabolism disorders in hypertension"],"prefix":"10.3389","volume":"13","author":[{"given":"Jing-wen","family":"Yue","sequence":"first","affiliation":[{"name":"Traditional Medicine Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-feng","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Traditional Medicine Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global burden of 87 risk factors in 204 countries and territories, 1990\u20132019: a systematic analysis for the global burden of disease study 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