ArticleBasic research in cardiology2018
LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling.
Article in Basic research in cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Guidelines for in vivo mouse models of myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2021Guideline
- Macrophages and the Survival of Cardiomyocytes After Myocardial Infarction.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Cellular and molecular signals of cardiac wound healing after myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2026Review
- GATA4-overexpressing BMSCs-derived exosome regulation of myocardial infarction in mice by key miRNA and apoptosis gene CLU.European journal of medical research · 2026Article
- Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease.Frontiers in immunology · 2026Review
- Cross-Talk Between Neutrophils and Macrophages Post-Myocardial Infarction: From Inflammatory Drivers to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Sex differences in the chronic autoimmune response to myocardial infarction.Clinical science (London, England : 1979) · 2025Article
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow.Nature communications · 2025Article
- Single-cell transcriptome unveils unique transcriptomic signatures of human organ-specific endothelial cells.Basic research in cardiology · 2024Article
- Sex Influences the Safety and Therapeutic Efficacy of Cardiac Nanomedicine Technologies.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Increased [Basic research in cardiology · 2024Article
- Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.American journal of physiology. Cell physiology · 2024Article
- Differences between human male and female neutrophils in mRNA, translation efficiency, protein, and phosphoprotein profiles.Research square · 2024Article
- Neutrophils are indispensable for adverse cardiac remodeling in heart failure.Journal of molecular and cellular cardiology · 2024Article
- Liver X Receptor Agonist 4β-Hydroxycholesterol as a Prognostic Factor in Coronary Artery Disease.Journal of the American Heart Association · 2024Observational
- Implications for neutrophils in cardiac arrhythmias.American journal of physiology. Heart and circulatory physiology · 2024Review
- Impact of age and sex on myelopoiesis and inflammation during myocardial infarction.Journal of molecular and cellular cardiology · 2024Review
- Guidelines on the use of sex and gender in cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2024Review
- Neutrophil-derived cathelicidin promotes cerebral angiogenesis after ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Sex differences in heart failure development following myocardial infarction (MI) are not fully understood. We hypothesized that differential MI signaling could explain variations in outcomes. Analysis of the mouse heart attack research tool 1.0 (422 mice; young = 5.4 ± 0.1; old = 23.3 ± 0.1 months of age) was used to dissect MI signaling pathways, which was validated in a new cohort of mice (4.8 ± 0.2 months of age); and substantiated in humans. Plasma collected at visit 2 from the MI subset of the Jackson Heart Study (JHS; a community-based study consisting of middle aged and older adults of African ancestry) underwent glycoproteomics grouped by outcome: (1) heart failure hospitalization after visit 2 (n = 3 men/12 women) and (2) without hospitalization through 2012 (n = 24 men/21 women). Compared to young male mice, the infarct region of young females had fewer, but more efficient tissue clearing neutrophils with reduced pro-inflammatory gene expression. Apolipoprotein (Apo) F, which acts upstream of the liver X receptors/retinoid X receptor (LXR/RXR) pathway, was elevated in the day 7 infarcts of old mice compared to young controls and was increased in both men and women with heart failure. In vitro, Apo F stimulated CD36 and peroxisome proliferator-activated receptor (PPAR)γ activation in male neutrophils to turn off NF-κB activation and stimulate LXR/RXR signaling to initiate resolution. Female neutrophils were desensitized to Apo F and instead relied on thrombospondin-1 stimulation of CD36 to upregulate AMP-activated protein kinase, resulting in an overall better wound healing strategy. With age, female mice were desensitized to LXR/RXR signaling, resulting in enhanced interleukin-6 activation, a finding replicated in the JHS community cohort. This is the first report to uncover sex differences in post-MI neutrophil signaling that yielded better outcomes in young females and worse outcomes with age.
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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.