ArticleNature metabolism2023
CRAT links cholesterol metabolism to innate immune responses in the heart.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 48 citations in OpenAlex.
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- Research on the effect of augmented reality based sensory interaction device in rehabilitation training of patients with chronic heart failure.BMC cardiovascular disorders · 2026Article
- Altered Carnitine Homeostasis Modulates Hyperosmolarity-Induced Mitochondrial Dysfunction and Lipotoxicity in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection.Transplantation direct · 2026Article
- The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor.Journal of translational medicine · 2026Review
- Mitochondrial homeostasis and aging: the mtDNA-cGAS-STING axis.Frontiers in immunology · 2026Review
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- DHCR24 Deficiency Drives Age-Related Meibomian Gland Dysfunction by Regulating Lipid Metabolic Imbalance and Cytosolic mtDNA-Induced cGAS-STING Activation.International journal of biological sciences · 2026Article
- Emerging insights of bile acids in cardiovascular physiology and disease: from molecular mechanisms to therapeutic potential.Frontiers in pharmacology · 2026Review
- Decoding the impact of gut microbiota on heart failure.Genes & diseases · 2025Review
- Bridging metabolism and immuno-inflammation: a novel framework to characterize dilated cardiomyopathy subtype.Journal of translational medicine · 2025Article
- From Gut to Heart: Targeting Trimethylamine N-Oxide as a Novel Strategy in Heart Failure Management.Biomolecules · 2025Review
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Identification and analysis of pyroptosis-related key genes in heart failure.Journal of cardiothoracic surgery · 2025Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic inflammation is associated with increased risk and poor prognosis of heart failure; however, the precise mechanism that provokes sustained inflammation in the failing heart remains elusive. Here we report that depletion of carnitine acetyltransferase (CRAT) promotes cholesterol catabolism through bile acid synthesis pathway in cardiomyocytes. Intracellular accumulation of bile acid or intermediate, 7α-hydroxyl-3-oxo-4-cholestenoic acid, induces mitochondrial DNA stress and triggers cGAS-STING-dependent type I interferon responses. Furthermore, type I interferon responses elicited by CRAT deficiency substantially increase AIM2 expression and AIM2-dependent inflammasome activation. Genetic deletion of cardiomyocyte CRAT in mice of both sexes results in myocardial inflammation and dilated cardiomyopathy, which can be reversed by combined depletion of caspase-1, cGAS or AIM2. Collectively, we identify a mechanism by which cardiac energy metabolism, cholesterol homeostasis and cardiomyocyte-intrinsic innate immune responses are interconnected via a CRAT-mediated bile acid synthesis pathway, which contributes to chronic myocardial inflammation and heart failure progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.