{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:51:22Z","timestamp":1793116282251,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Trimethylamine oxide (TMAO) is a newly found intestinal microbiota metabolite. Here, we aimed to explore the effects of TMAO on calcium homeostasis and its implication in cardiac hypertrophy, especially focusing on the regulatory mechanism of TMAO on the key calcium transporter SERCA2a. Echocardiography and histological assessment showed that mice fed with TMAO or Choline for 8 weeks exhibited significant pathological changes of cardiac hypertrophy, which is accompanied by increased plasma levels of TMAO. The results indicated that TMAO could increase the intracellular Ca<jats:sup>2+<\/jats:sup> level, up-regulate the expression of ANP and MYH7, and down-regulate SERCA2a expression, which could be reversed by overexpressing of SERCA2a and BAPTA-AM. Meanwhile, TMAO treatment promotes autophagy in vitro and in vivo. By employing immunofluorescence staining and immunoprecipitation assay, it was found that SERCA2a bound to ATG5 and transported to autophagosomes via the ATG5 complex for degradation under TMAO conditions. Furthermore, either 3MA or siATG5 could ameliorate TMAO-induced cardiomyocyte hypertrophy and SERCA2a degradation. Finally, in vivo intervention showed that 3MA could relieve cardiac hypertrophy and rescue the down-regulation of SERCA2a in TMAO-fed mice. The current study identifies a mechanism in which TMAO promotes cardiac hypertrophy via elevated intracellular Ca<jats:sup>2+<\/jats:sup> levels and enhanced autophagy degradation of SERCA2a.<\/jats:p>","DOI":"10.1038\/s42003-025-08016-9","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T15:28:37Z","timestamp":1744298917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The gut microbiota metabolite trimethylamine N-oxide promotes cardiac hypertrophy by activating the autophagic degradation of SERCA2a"],"prefix":"10.1038","volume":"8","author":[{"given":"Dongyu","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feilong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-8811","authenticated-orcid":false,"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"8016_CR1","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nm.3145","volume":"19","author":"RA Koeth","year":"2013","unstructured":"Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576\u2013585 (2013).","journal-title":"Nat. Med."},{"key":"8016_CR2","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.cell.2016.02.011","volume":"165","author":"W Zhu","year":"2016","unstructured":"Zhu, W. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165, 111\u2013124 (2016).","journal-title":"Cell"},{"key":"8016_CR3","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1016\/j.cell.2015.11.055","volume":"163","author":"Z Wang","year":"2015","unstructured":"Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585\u20131595 (2015).","journal-title":"Cell"},{"key":"8016_CR4","doi-asserted-by":"publisher","unstructured":"Jama, H. A., Beale, A., Shihata, W. A. & Marques, F. Z. The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism? Cardiovascular research 115, 1435-1447, https:\/\/doi.org\/10.1093\/cvr\/cvz091 (2019).","DOI":"10.1093\/cvr\/cvz091"},{"key":"8016_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.111156","volume":"134","author":"S Naqvi","year":"2021","unstructured":"Naqvi, S. et al. A cross-talk between gut microbiome, salt and hypertension. Biomedicine Pharmacother. = Biomedecine pharmacotherapie 134, (2021). 111156.","journal-title":"Biomedicine Pharmacother. = Biomedecine pharmacotherapie"},{"key":"8016_CR6","doi-asserted-by":"publisher","unstructured":"Verhaar, B. J. H., Prodan, A., Nieuwdorp, M. & Muller, M. Gut Microbiota in Hypertension and Atherosclerosis: A Review. Nutrients 12, https:\/\/doi.org\/10.3390\/nu12102982 (2020).","DOI":"10.3390\/nu12102982"},{"key":"8016_CR7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1161\/HYPERTENSIONAHA.120.14759","volume":"76","author":"VE Brunt","year":"2020","unstructured":"Brunt, V. E. et al. Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans. Hypertension (Dallas, Tex. : 1979) 76, 101\u2013112 (2020).","journal-title":"Hypertension (Dallas, Tex. : 1979)"},{"key":"8016_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.cardfail.2014.11.006","volume":"21","author":"WH Tang","year":"2015","unstructured":"Tang, W. H. et al. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J. Card. Fail. 21, 91\u201396 (2015).","journal-title":"J. Card. Fail."},{"key":"8016_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102115","volume":"46","author":"S Jiang","year":"2021","unstructured":"Jiang, S. et al. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II-induced hypertension. Redox Biol. 46, (2021). 102115.","journal-title":"Redox Biol."},{"key":"8016_CR10","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1073\/pnas.97.2.793","volume":"97","author":"MI Miyamoto","year":"2000","unstructured":"Miyamoto, M. I. et al. Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc. Natl Acad. Sci. USA 97, 793\u2013798 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"8016_CR11","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1161\/hc3601.095574","volume":"104","author":"F del Monte","year":"2001","unstructured":"del Monte, F. et al. Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure. Circulation 104, 1424\u20131429 (2001).","journal-title":"Circulation"},{"key":"8016_CR12","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1161\/CIRCULATIONAHA.111.022889","volume":"124","author":"M Jessup","year":"2011","unstructured":"Jessup, M. et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124, 304\u2013313 (2011).","journal-title":"Circulation"},{"key":"8016_CR13","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1161\/CIRCRESAHA.113.302421","volume":"114","author":"K Zsebo","year":"2014","unstructured":"Zsebo, K. et al. Long-term effects of AAV1\/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circulation Res. 114, 101\u2013108 (2014).","journal-title":"Circulation Res."},{"key":"8016_CR14","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/s41556-020-0554-4","volume":"22","author":"A Nowosad","year":"2020","unstructured":"Nowosad, A. et al. p27 controls Ragulator and mTOR activity in amino acid-deprived cells to regulate the autophagy-lysosomal pathway and coordinate cell cycle and cell growth. Nat. cell Biol. 22, 1076\u20131090 (2020).","journal-title":"Nat. cell Biol."},{"key":"8016_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153681","volume":"91","author":"W Fan","year":"2021","unstructured":"Fan, W. et al. Plantago asiatica L. seeds extract protects against cardiomyocyte injury in isoproterenol- induced cardiac hypertrophy by inhibiting excessive autophagy and apoptosis in mice. Phytomedicine : Int. J. Phytother. phytopharmacology 91, (2021). 153681.","journal-title":"Phytomedicine : Int. J. Phytother. phytopharmacology"},{"key":"8016_CR16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.freeradbiomed.2021.11.010","volume":"179","author":"F Dong","year":"2022","unstructured":"Dong, F. et al. Trimethylamine N-oxide promotes hyperoxaluria-induced calcium oxalate deposition and kidney injury by activating autophagy. Free Radic. Biol. Med. 179, 288\u2013300 (2022).","journal-title":"Free Radic. Biol. Med."},{"key":"8016_CR17","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1093\/cvr\/cvz205","volume":"116","author":"H Hu","year":"2020","unstructured":"Hu, H. et al. HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling. Cardiovascular Res. 116, 944\u2013955 (2020).","journal-title":"Cardiovascular Res."},{"key":"8016_CR18","doi-asserted-by":"crossref","unstructured":"Zeng, Y. et al. Gut Microbiota-Derived Trimethylamine N-Oxide and Kidney Function: A Systematic Review and Meta-Analysis. Adv. Nutr. (Bethesda, Md) 12, 1286\u20131304 (2021).","DOI":"10.1093\/advances\/nmab010"},{"key":"8016_CR19","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1161\/STROKEAHA.120.031443","volume":"53","author":"J Xu","year":"2022","unstructured":"Xu, J. et al. Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes. Stroke 53, 1207\u20131215 (2022).","journal-title":"Stroke"},{"key":"8016_CR20","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1093\/nutrit\/nuaa111","volume":"79","author":"M Abbasalizad Farhangi","year":"2021","unstructured":"Abbasalizad Farhangi, M. & Vajdi, M. Gut microbiota-associated trimethylamine N-oxide and increased cardiometabolic risk in adults: a systematic review and dose-response meta-analysis. Nutr. Rev. 79, 1022\u20131042 (2021).","journal-title":"Nutr. Rev."},{"key":"8016_CR21","doi-asserted-by":"publisher","unstructured":"Bin-Jumah, M. N. et al. Pathobiological Relationship of Excessive Dietary Intake of Choline\/L-Carnitine: A TMAO Precursor-Associated Aggravation in Heart Failure in Sarcopenic Patients. Nutrients 13, https:\/\/doi.org\/10.3390\/nu13103453 (2021).","DOI":"10.3390\/nu13103453"},{"key":"8016_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-1-4615-2946-0_9","volume":"346","author":"G Hasenfuss","year":"1993","unstructured":"Hasenfuss, G., Pieske, B., Holubarsch, C., Alpert, N. R. & Just, H. Excitation-contraction coupling and contractile protein function in failing and nonfailing human myocardium. Adv. Exp. Med. Biol. 346, 91\u2013100 (1993).","journal-title":"Adv. Exp. Med. Biol."},{"key":"8016_CR23","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJM199108293250906","volume":"325","author":"JP Morgan","year":"1991","unstructured":"Morgan, J. P. Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction.  N. Engl. J. Med. 325, 625\u2013632 (1991).","journal-title":"N. Engl. J. Med."},{"key":"8016_CR24","doi-asserted-by":"publisher","first-page":"9496","DOI":"10.1111\/jcmm.16941","volume":"25","author":"J Nan","year":"2021","unstructured":"Nan, J. et al. The interplay between mitochondria and store-operated Ca(2+) entry: Emerging insights into cardiac diseases. J. Cell. Mol. Med. 25, 9496\u20139512 (2021).","journal-title":"J. Cell. Mol. Med."},{"key":"8016_CR25","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1007\/s12012-021-09654-1","volume":"21","author":"BE Yamasan","year":"2021","unstructured":"Yamasan, B. E., Mercan, T., Erkan, O. & Ozdemir, S. Ellagic Acid Prevents Ca(2+) Dysregulation and Improves Functional Abnormalities of Ventricular Myocytes via Attenuation of Oxidative Stress in Pathological Cardiac Hypertrophy. Cardiovascular Toxicol. 21, 630\u2013641 (2021).","journal-title":"Cardiovascular Toxicol."},{"key":"8016_CR26","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.ceca.2011.04.001","volume":"50","author":"JP Decuypere","year":"2011","unstructured":"Decuypere, J. P., Bultynck, G. & Parys, J. B. A dual role for Ca(2+) in autophagy regulation. Cell calcium 50, 242\u2013250 (2011).","journal-title":"Cell calcium"},{"key":"8016_CR27","doi-asserted-by":"publisher","first-page":"3640","DOI":"10.1007\/s00018-008-8383-9","volume":"65","author":"SH Wang","year":"2008","unstructured":"Wang, S. H., Shih, Y. L., Ko, W. C., Wei, Y. H. & Shih, C. M. Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell. Mol. life Sci. : CMLS 65, 3640\u20133652 (2008).","journal-title":"Cell. Mol. life Sci. : CMLS"},{"key":"8016_CR28","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1536\/ihj.19-372","volume":"61","author":"B Jin","year":"2020","unstructured":"Jin, B. et al. Destructive Role of TMAO in T-Tubule and Excitation-Contraction Coupling in the Adult Cardiomyocytes. Int. heart J. 61, 355\u2013363 (2020).","journal-title":"Int. heart J."},{"key":"8016_CR29","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1161\/CIRCULATIONAHA.120.053365","volume":"144","author":"M Korf-Klingebiel","year":"2021","unstructured":"Korf-Klingebiel, M. et al. Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving Sarco\/Endoplasmic Reticulum Ca(2+)-ATPase Expression in Cardiomyocytes. Circulation 144, 1227\u20131240 (2021).","journal-title":"Circulation"},{"key":"8016_CR30","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1038\/s41401-020-00580-6","volume":"42","author":"GL Xue","year":"2021","unstructured":"Xue, G. L. et al. Interleukin-17 upregulation participates in the pathogenesis of heart failure in mice via NF-\u03baB-dependent suppression of SERCA2a and Cav1.2 expression. Acta pharmacologica Sin. 42, 1780\u20131789 (2021).","journal-title":"Acta pharmacologica Sin."},{"key":"8016_CR31","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1002\/ejhf.826","volume":"19","author":"JS Hulot","year":"2017","unstructured":"Hulot, J. S. et al. Effect of intracoronary administration of AAV1\/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial. Eur. J. heart Fail. 19, 1534\u20131541 (2017).","journal-title":"Eur. J. heart Fail."},{"key":"8016_CR32","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1161\/HYPERTENSIONAHA.119.12998","volume":"74","author":"B Cai","year":"2019","unstructured":"Cai, B. et al. Long Noncoding RNA-DACH1 (Dachshund Homolog 1) Regulates Cardiac Function by Inhibiting SERCA2a (Sarcoplasmic Reticulum Calcium ATPase 2a). Hypertension (Dallas, Tex. : 1979) 74, 833\u2013842 (2019).","journal-title":"Hypertension (Dallas, Tex. : 1979)"},{"key":"8016_CR33","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.7150\/ijbs.48437","volume":"16","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. et al. E3 Ubiquitin ligase NEDD4 family\u2011regulatory network in cardiovascular disease. Int. J. Biol. Sci. 16, 2727\u20132740 (2020).","journal-title":"Int. J. Biol. Sci."},{"key":"8016_CR34","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41574-021-00551-9","volume":"17","author":"M Kitada","year":"2021","unstructured":"Kitada, M. & Koya, D. Autophagy in metabolic disease and ageing. Nat. Rev. Endocrinol. 17, 647\u2013661 (2021).","journal-title":"Nat. Rev. Endocrinol."},{"key":"8016_CR35","doi-asserted-by":"publisher","first-page":"5284","DOI":"10.1172\/JCI70877","volume":"123","author":"MS Bhuiyan","year":"2013","unstructured":"Bhuiyan, M. S. et al. Enhanced autophagy ameliorates cardiac proteinopathy.  J. Clin. Investig. 123, 5284\u20135297 (2013).","journal-title":"J. Clin. Investig."},{"key":"8016_CR36","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/aps.2014.45","volume":"35","author":"LQ Weng","year":"2014","unstructured":"Weng, L. Q. et al. Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice. Acta pharmacologica Sin. 35, 1005\u20131014 (2014).","journal-title":"Acta pharmacologica Sin."},{"key":"8016_CR37","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.freeradbiomed.2021.09.008","volume":"175","author":"C Zhao","year":"2021","unstructured":"Zhao, C. et al. Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells. Free Radic. Biol. Med. 175, 236\u2013248 (2021).","journal-title":"Free Radic. Biol. Med."},{"key":"8016_CR38","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1016\/j.immuni.2021.07.012","volume":"54","author":"N Reglero-Real","year":"2021","unstructured":"Reglero-Real, N. et al. Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation. Immunity 54, 1989\u20132004.e1989 (2021).","journal-title":"Immunity"},{"key":"8016_CR39","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/s41419-021-04059-y","volume":"12","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy. Cell death Dis. 12, 1069 (2021).","journal-title":"Cell death Dis."},{"key":"8016_CR40","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1080\/10286020.2021.2024810","volume":"24","author":"Y Zeng","year":"2022","unstructured":"Zeng, Y. et al. Autophagy and pressure overload-induced cardiac hypertrophy. J. Asian Nat. products Res. 24, 1101\u20131108 (2022).","journal-title":"J. Asian Nat. products Res."},{"key":"8016_CR41","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/FJC.0b013e3182646cb1","volume":"60","author":"OF Rifki","year":"2012","unstructured":"Rifki, O. F. & Hill, J. A. Cardiac autophagy: good with the bad. J. cardiovascular Pharmacol. 60, 248\u2013252 (2012).","journal-title":"J. cardiovascular Pharmacol."},{"key":"8016_CR42","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1093\/cvr\/cvab158","volume":"118","author":"D Gatica","year":"2022","unstructured":"Gatica, D., Chiong, M., Lavandero, S. & Klionsky, D. J. The role of autophagy in cardiovascular pathology. Cardiovascular Res. 118, 934\u2013950 (2022).","journal-title":"Cardiovascular Res."},{"key":"8016_CR43","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3389\/fnmol.2020.00138","volume":"13","author":"M Govindarajulu","year":"2020","unstructured":"Govindarajulu, M. et al. Gut Metabolite TMAO Induces Synaptic Plasticity Deficits by Promoting Endoplasmic Reticulum Stress. Front. Mol. Neurosci. 13, 138 (2020).","journal-title":"Front. Mol. Neurosci."},{"key":"8016_CR44","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1093\/cvr\/cvab243","volume":"118","author":"J Li","year":"2022","unstructured":"Li, J. et al. Trimethylamine N-oxide induces osteogenic responses in human aortic valve interstitial cells in vitro and aggravates aortic valve lesions in mice. Cardiovascular Res. 118, 2018\u20132030 (2022).","journal-title":"Cardiovascular Res."},{"key":"8016_CR45","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.biopha.2017.11.016","volume":"97","author":"J Geng","year":"2018","unstructured":"Geng, J. et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK\/JNK pathway. Biomedicine Pharmacother. = Biomedecine pharmacotherapie 97, 941\u2013947 (2018).","journal-title":"Biomedicine Pharmacother. = Biomedecine pharmacotherapie"},{"key":"8016_CR46","doi-asserted-by":"publisher","unstructured":"Querio, G., Antoniotti, S., Geddo, F., Levi, R. & Gallo, M. P. Trimethylamine N-Oxide (TMAO) Impairs Purinergic Induced Intracellular Calcium Increase and Nitric Oxide Release in Endothelial Cells. International journal of molecular sciences 23, https:\/\/doi.org\/10.3390\/ijms23073982 (2022).","DOI":"10.3390\/ijms23073982"},{"key":"8016_CR47","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13578-021-00661-x","volume":"11","author":"X Chen","year":"2021","unstructured":"Chen, X. et al. Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases. Cell Biosci. 11, 147 (2021).","journal-title":"Cell Biosci."},{"key":"8016_CR48","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau0495","volume":"5","author":"X Xie","year":"2019","unstructured":"Xie, X. et al. The immunoproteasome catalytic \u03b25i subunit regulates cardiac hypertrophy by targeting the autophagy protein ATG5 for degradation. Sci. Adv. 5, (2019). eaau0495.","journal-title":"Sci. Adv."},{"key":"8016_CR49","doi-asserted-by":"publisher","unstructured":"Chen, R. J. et al. Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE\/STAT3 Pathway. Molecules (Basel, Switzerland) 26, https:\/\/doi.org\/10.3390\/molecules26216741 (2021).","DOI":"10.3390\/molecules26216741"},{"key":"8016_CR50","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1161\/CIRCRESAHA.111.300483","volume":"112","author":"L Long","year":"2013","unstructured":"Long, L. et al. Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation. Circulation Res. 112, 1159\u20131170 (2013).","journal-title":"Circulation Res."},{"key":"8016_CR51","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1080\/15548627.2020.1851897","volume":"17","author":"Z Yang","year":"2021","unstructured":"Yang, Z. et al. Autophagy alleviates hypoxia-induced blood-brain barrier injury via regulation of CLDN5 (claudin 5). Autophagy 17, 3048\u20133067 (2021).","journal-title":"Autophagy"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08016-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08016-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08016-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T17:02:56Z","timestamp":1744304576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08016-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8016"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08016-9","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"7 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"596"}}