ArticleJournal of molecular and cellular cardiology2016
CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.Cellular and molecular life sciences : CMLS · 2024Pooled it
- Article
- Obesity-Associated Cardiac Fibrosis: Mechanisms and Emerging Therapeutic Targets.Vascular health and risk management · 2026Review
- The RhoGDIβ-Rac1-CARD9 Signaling Module Mediates Islet β-Cell Dysfunction Under Chronic Hyperglycemia.Cells · 2025Review
- Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.International journal of biological sciences · 2025Article
- Role of bariatric surgery in improving diabetic cardiomyopathy: Molecular mechanisms and therapeutic perspectives (Review).Molecular medicine reports · 2024Review
- Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling.Clinical and translational medicine · 2024Article
- Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?Biochemical pharmacology · 2023Review
- Targeting mitochondrial shape: at the heart of cardioprotection.Basic research in cardiology · 2023Article
- Regulatory Roles of Histone Deacetylation in Metabolic Stress-Induced Expression of Caspase Recruitment Domain-Containing Protein 9 (CARD9) in Pancreatic β-Cells.International journal of molecular sciences · 2023Article
- Macrophage CARD9 mediates cardiac injury following myocardial infarction through regulation of lipocalin 2 expression.Signal transduction and targeted therapy · 2023Article
- CARD9 deficiency improves the recovery of limb ischemia in mice with ambient fine particulate matter exposure.Frontiers in cardiovascular medicine · 2023Article
- Article
- Dysregulated lipolysis and lipophagy in lipid droplets of macrophages from high fat diet-fed obese mice.Journal of cellular and molecular medicine · 2022Article
- Triptolide promotes autophagy to inhibit mesangial cell proliferation in IgA nephropathy via the CARD9/p38 MAPK pathway.Cell proliferation · 2022Article
- CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- CARD9 Signaling, Inflammation, and Diseases.Frontiers in immunology · 2022Review
- CARD9 Regulation and its Role in Cardiovascular Diseases.International journal of biological sciences · 2022Review
- Effects ofNutrition research and practice · 2021Article
- Functional resilience of C57BL/6J mouse heart to dietary fat overload.American journal of physiology. Heart and circulatory physiology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart.
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Registered trials
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.