{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:04:33Z","timestamp":1780416273761,"version":"3.54.1"},"reference-count":37,"publisher":"Sociedade Brasileira de Cardiologia","issue":"4","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Bras. Cardiol."],"abstract":"<jats:p>Resumo  Fundamento  O infarto do mioc\u00e1rdio (IM), um evento cardiovascular agudo, tem sido associado, em estudos anteriores, a respostas imunes e metab\u00f3litos. No entanto, a rela\u00e7\u00e3o causal entre c\u00e9lulas imunes e IM, bem como o papel mediador dos metab\u00f3litos plasm\u00e1ticos, ainda n\u00e3o foram claramente confirmados.  Objetivos  An\u00e1lise sistem\u00e1tica da associa\u00e7\u00e3o causal entre 731 c\u00e9lulas imunes e IM, bem como os pap\u00e9is mediadores de 1400 metab\u00f3litos plasm\u00e1ticos.  M\u00e9todos  A an\u00e1lise de randomiza\u00e7\u00e3o mendeliana (RM) bidirecional foi utilizada para explorar a rela\u00e7\u00e3o causal entre c\u00e9lulas imunes e IM, e an\u00e1lises de media\u00e7\u00e3o em uma e duas etapas foram realizadas para identificar metab\u00f3litos plasm\u00e1ticos. Os m\u00e9todos de an\u00e1lise inclu\u00edram vari\u00e2ncia inversa ponderada (VIP) (p&lt;0,05), mediana ponderada (p&lt;0,05), moda simples (p&lt;0,05), moda ponderada (p&lt;0,05), regress\u00e3o MR-Egger (p&lt;0,05), intercepto MR-Egger (p&gt;0,05) e MR-PRESSO (p&gt;0,05) para avaliar a confiabilidade dos resultados. Os SNPs associados a c\u00e9lulas imunes e metab\u00f3litos foram submetidos \u00e0 sele\u00e7\u00e3o de genes utilizando o banco de dados STRING, seguida por an\u00e1lise de enriquecimento.  Resultados  Um total de 44 c\u00e9lulas imunes foram identificadas com associa\u00e7\u00e3o causal com o IM (p&lt;0,05), dentre as quais o HLA DR em c\u00e9lulas dendr\u00edticas (ebi-a-GCST90002106) apresentou a signific\u00e2ncia mais forte (p&lt;0,001). Um total de 19 SNPs foram identificados (OR=1,038, IC 95% 1,018-1,059). A an\u00e1lise reversa n\u00e3o mostrou signific\u00e2ncia estat\u00edstica (p&gt;0,05). Metab\u00f3litos plasm\u00e1ticos, incluindo os n\u00edveis de glicuron\u00eddeo de \u00e1cido deoxic\u00f3lico, a raz\u00e3o fosfato\/N-acetilneuraminato e a glicosilceramida, desempenharam um papel mediador entre as c\u00e9lulas imunes e o IM, com efeitos de media\u00e7\u00e3o de 7,0%, 4,6% e 6,6%, respectivamente. A an\u00e1lise do banco de dados STRING identificou oito genes-chave e uma via de sinaliza\u00e7\u00e3o que potencialmente conectam os fen\u00f3tipos imunes e os tr\u00eas metab\u00f3litos (p&lt;0,05).  Conclus\u00f5es  Este estudo identificou uma rela\u00e7\u00e3o causal entre c\u00e9lulas imunes e IM. Os metab\u00f3litos n\u00edveis de glicuron\u00eddeo de \u00e1cido deoxic\u00f3lico, raz\u00e3o fosfato\/N-acetilneuraminato e glicosilceramida desempenharam um papel mediador parcial nessa rela\u00e7\u00e3o causal.<\/jats:p>","DOI":"10.36660\/abc.20250026","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:10:12Z","timestamp":1780413012000},"source":"Crossref","is-referenced-by-count":0,"title":["Associa\u00e7\u00e3o Causal entre C\u00e9lulas Imunes Mediadas por Metab\u00f3litos Plasm\u00e1ticos e Infarto do Mioc\u00e1rdio: Um Estudo de Randomiza\u00e7\u00e3o Mendeliana"],"prefix":"10.36660","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4741-435X","authenticated-orcid":false,"given":"Yue","family":"Liu","sequence":"first","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicin,  China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22636","published-online":{"date-parts":[[2026]]},"reference":[{"issue":"1","key":"ref1","article-title":"Signaling Pathways and Targeted Therapy for Myocardial Infarction","volume":"7","author":"Zhang Q","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"ref2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1084460","article-title":"The Role of Major Immune Cells in Myocardial Infarction","volume":"13","author":"Feng Q","year":"2023","journal-title":"Front Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.2147\/JIR.S416914","article-title":"Identifying Immune Cell Infiltration and Hub Genes during the Myocardial Remodeling Process after Myocardial Infarction","volume":"16","author":"Tian Y","year":"2023","journal-title":"J Inflamm Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jad.2023.08.098","article-title":"Causal Relationships between Dietary Habits and Five Major Mental Disorders: A Two-Sample Mendelian Randomization Study","volume":"340","author":"Du Z","year":"2023","journal-title":"J Affect Disord"},{"issue":"10","key":"ref5","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1038\/s41588-020-0684-4","article-title":"Complex Genetic Signatures in Immune Cells Underlie Autoimmunity and Inform Therapy","volume":"52","author":"Orr\u00f9 V","year":"2020","journal-title":"Nat Genet"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/ng.3368","article-title":"Genome Sequencing Elucidates Sardinian Genetic Architecture and Augments Association Analyses for Lipid and Blood Inflammatory Markers","volume":"47","author":"Sidore C","year":"2015","journal-title":"Nat Genet"},{"key":"ref7","article-title":"Causal Role of Immune Cell Phenotypes in Idiopathic Sudden Sensorineural Hearing Loss: A Bi-Directional Mendelian Randomization Study","volume":"15","author":"Li W","year":"2024","journal-title":"Front Neurol"},{"key":"ref8","article-title":"Exploration of the Causal Associations between Circulating Inflammatory Proteins, Immune Cells, and Neuromyelitis Optica Spectrum Disorder: A Bidirectional Mendelian Randomization Study and Mediation Analysis","volume":"16","author":"Chen Z","year":"2024","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"ref9","article-title":"Association between Gut Microbiota and Preeclampsia-Eclampsia: A Two-Sample Mendelian Randomization Study","volume":"20","author":"Li P","year":"2022","journal-title":"BMC Med"},{"key":"ref10","article-title":"Investigating the Causal Relationship and Potential Shared Diagnostic Genes between Primary Biliary Cholangitis and Systemic Lupus Erythematosus Using Bidirectional Mendelian Randomization and Transcriptomic Analyses","volume":"15","author":"Tao T","year":"2024","journal-title":"Front 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Cells: Effective Killers Suspected for Antigen Presentation","volume":"109","author":"Erokhina SA","year":"2021","journal-title":"J Leukoc Biol"},{"key":"ref15","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.636188","article-title":"HMGB1 Activates Myeloid Dendritic Cells by Up-Regulating mTOR Pathway in Systemic Lupus Erythematosus","volume":"8","author":"Song X","year":"2021","journal-title":"Front Med"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1111\/jcmm.15154","article-title":"Coronary Artery Bypass Grafting is Associated with Immunoparalysis of Monocytes and Dendritic Cells","volume":"24","author":"Perros AJ","year":"2020","journal-title":"J Cell Mol Med"},{"key":"ref17","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1210961","article-title":"Proinflammatory Role of Monocytes in SARS-CoV-2 Infection in Chronic Hemodialysis Patients","volume":"14","author":"Bumbea V","year":"2023","journal-title":"Front 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Study","volume":"11","author":"Ye Q","year":"2024","journal-title":"Front Nutr"},{"key":"ref22","first-page":"1","article-title":"Utilizing Serum and Urine Metabolomics for Diagnosing Acute Intra- Abdominal Infection in the Early Stage","author":"Dong Z","year":"2024","journal-title":"Res Sq"},{"issue":"15","key":"ref23","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.023024","article-title":"Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study","volume":"11","author":"Campos-Obando N","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5551\/jat.RV22012","article-title":"Phosphate and Coronary Artery Disease in Patients with Chronic Kidney Disease","volume":"31","author":"Ogata H","year":"2024","journal-title":"J Atheroscler Thromb"},{"issue":"5","key":"ref25","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/jdi.14189","article-title":"Common Metabolite for Microangiopathy in Japanese and European Populations","volume":"15","author":"Shojima N","year":"2024","journal-title":"J Diabetes Investig"},{"issue":"20","key":"ref26","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1016\/j.jacc.2021.03.314","article-title":"Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients with Cardiovascular Disease","volume":"77","author":"Akawi N","year":"2021","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.43854","article-title":"Plasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study","volume":"6","author":"Bockus LB","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"10","key":"ref28","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110475","article-title":"Mutant CHCHD10 Causes an Extensive Metabolic Rewiring that Precedes OXPHOS Dysfunction in a Murine Model of Mitochondrial Cardiomyopathy","volume":"38","author":"Sayles NM","year":"2022","journal-title":"Cell Rep"},{"key":"ref29","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2023.1185284","article-title":"Gene Expression Signatures Associated with Chronic Endometritis Revealed by RNA Sequencing","volume":"10","author":"Oshina K","year":"2023","journal-title":"Front Med"},{"issue":"1","key":"ref30","article-title":"Aberrant Splicing of CaV1.2 Calcium Channel Induced by Decreased Rbfox1 Enhances Arterial Constriction during Diabetic Hyperglycemia","volume":"81","author":"Hou W","year":"2024","journal-title":"Cell Mol Life Sci"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1161\/CIRCRESAHA.122.321692","article-title":"FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells","volume":"132","author":"Wong D","year":"2023","journal-title":"Circ Res"},{"issue":"11","key":"ref32","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.168836","article-title":"The Effect of Dnaaf5 Gene Dosage on Primary Ciliary Dyskinesia Phenotypes","volume":"8","author":"Horani A","year":"2023","journal-title":"JCI Insight"},{"issue":"2","key":"ref33","article-title":"Steroid-Sensitive Nephrotic Syndrome Candidate Gene CLVS1 Regulates Podocyte Oxidative Stress and Endocytosis","volume":"7","author":"Lane BM","year":"2022","journal-title":"JCI Insight"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2024.2388306","article-title":"FCGR3A F158V Alleles Frequency Differs in Multiple Myeloma Patients from Healthy Population","volume":"13","author":"Constantinides 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