ArticleScientific reports2018
Hepatokine α1-Microglobulin Signaling Exacerbates Inflammation and Disturbs Fibrotic Repair in Mouse Myocardial Infarction.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Omics data discovery agents: Agent-supported retrieval, reanalysis, and synthesis of published omics data.PLoS computational biology · 2026Article
- Omics Data Discovery Agents: Agent-Supported Retrieval, Reanalysis, and Synthesis of Published Omics Data.ArXiv · 2026Article
- Article
- Changes in the Lipidome Are Associated With Immune Activation and Subclinical Vascular Disease in Youth With Human Immunodeficiency Virus in Uganda.The Journal of infectious diseases · 2025Article
- Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.Journal of clinical and translational hepatology · 2023Review
- Phospholipids, the Masters in the Shadows during Healing after Acute Myocardial Infarction.International journal of molecular sciences · 2023Review
- Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines.Antioxidants (Basel, Switzerland) · 2023Review
- Urinary Alpha1-Microglobulin: A New Predictor for In-Hospital Mortality in Patients with ST-Segment Elevation Myocardial Infarction.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Organ-organ communication: The liver's perspective.Theranostics · 2021Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute cardiac rupture and adverse left ventricular (LV) remodeling causing heart failure are serious complications of acute myocardial infarction (MI). While cardio-hepatic interactions have been recognized, their role in MI remains unknown. We treated cultured cardiomyocytes with conditioned media from various cell types and analyzed the media by mass spectrometry to identify α1-microglobulin (AM) as an Akt-activating hepatokine. In mouse MI model, AM protein transiently distributed in the infarct and border zones during the acute phase, reflecting infiltration of AM-bound macrophages. AM stimulation activated Akt, NFκB, and ERK signaling and enhanced inflammation as well as macrophage migration and polarization, while inhibited fibrogenesis-related mRNA expression in cultured macrophages and cardiac fibroblasts. Intramyocardial AM administration exacerbated macrophage infiltration, inflammation, and matrix metalloproteinase 9 mRNA expression in the infarct and border zones, whereas disturbed fibrotic repair, then provoked acute cardiac rupture in MI. Shotgun proteomics and lipid pull-down analysis found that AM partly binds to phosphatidic acid (PA) for its signaling and function. Furthermore, systemic delivery of a selective inhibitor of diacylglycerol kinase α-mediated PA synthesis notably reduced macrophage infiltration, inflammation, matrix metalloproteinase activity, and adverse LV remodeling in MI. Therefore, targeting AM signaling could be a novel pharmacological option to mitigate adverse LV remodeling in MI.
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