Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort

Katra, Pernilla; Hennings, Viktoria; Nilsson, Jan; Engström, Gunnar; Engelbertsen, Daniel; Bengtsson, Eva; Björkbacka, Harry

doi:10.1016/j.atherosclerosis.2023.01.004

Cited by 4 publications

(2 citation statements)

References 29 publications

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“… 20 Although there are a large number of literatures proving the role of CCL19 in atherosclerosis, there are also literatures indicating that CCL19 cannot be used as a predictor of future adverse events in coronary heart disease population. 21 Our research also shows that CCL19 is higher in male atherosclerosis patients than in women. CXCR1 is a member of the G-protein-coupled receptor family.…”

Section: Discussionsupporting

confidence: 62%

Immune-Related Genes in the Pathogenesis of Atherosclerosis: Based on Sex Differences

Zhang,

Lin,

Guo

et al. 2023

JIR

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Purpose Atherosclerosis is still a global public problem with increasing incidence rate and mortality. It has been found that gender factors play an important role in the progression of atherosclerosis. However, few people explore gender related atherosclerosis at the level of genes and immune cells. The purpose of this study was to determine genetic and immune cell differences between male and female samples. Patients and Methods This study aims to identify differential genes between male and female samples in the GSE43292 dataset. The focus will be on identifying immune-related genes (IRGs) among these differentially expressed genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis will be employed to explore the enrichment of IRGs in biological processes, molecular functions, cellular components, and pathways. Furthermore, a protein-protein interaction (PPI) network for the IRGs will be constructed using Cytoscape software. To estimate the degree of immune cell infiltration, single-sample gene set enrichment analysis (ssGSEA) will be conducted. Moreover, the identified IRGs will be validated using GSE28829 dataset. Finally, we validated in atherosclerotic mice. Results Seven IRGs (CCL13, IL1RN, FPR2, S100A8, CCL19, CXCL1, CXCL8) were identified as being overexpressed in male atherosclerosis. GO and KEGG analysis revealed that these IRGs are primarily enriched in inflammatory response pathways, cytokine signaling pathways, and cytokine- cytokine receptor interactions. Notably, when compared to females, there was a significant infiltration of immune cells in male specimens. Importantly, all seven IRGs demonstrated high diagnostic value in GSE28829 dataset. The use of animal samples supports our results. Conclusion This study demonstrates the effectiveness of seven IRGs and reveal sex differences in atherosclerosis. Notably, there is a significant presence of immune cells within the atherosclerotic plaque of men compared to women. These findings have potential implications for the development of personalized treatment approaches targeting gender-related atherosclerosis.

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Section: Discussionsupporting

confidence: 62%

Immune-Related Genes in the Pathogenesis of Atherosclerosis: Based on Sex Differences

Zhang,

Lin,

Guo

et al. 2023

JIR

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“…[58][59][60] C-C motif chemokine ligand 21c (Ccl21c), a chemokine involved in immune cell trafficking, has been implicated in atherosclerosis, myocardial infarction, and heart failure in patients. [61][62][63] Increased levels of CCL21 have been detected in ruptured lesions in the coronary arteries of patients with myocardial infarction 64 and in explanted myocardial tissue from patients with heart failure. 62 Interestingly, although Dox treatment has been associated with a robust inflammatory response in the heart, WT mice treated with Dox demonstrated downregulation of Ccl21c.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cyp1a Protects Mice against Anthracycline Cardiomyopathy

Liu,

Curtin,

Lall

et al. 2024

Preprint

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Background: Anthracyclines such as doxorubicin (Dox) are highly effective anti-tumor agents, but their use is limited by dose-dependent cardiomyopathy and heart failure. Our laboratory previously reported that induction of cytochrome P450 family 1 (Cyp1) enzymes contributes to acute Dox cardiotoxicity in zebrafish and in mice, and that potent Cyp1 inhibitors prevent cardiotoxicity. However, the role of Cyp1 enzymes in chronic Dox cardiomyopathy, as well as the mechanisms underlying cardioprotection associated with Cyp1 inhibition, have not been fully elucidated. Methods: The Cyp1 pathway was evaluated using a small molecule Cyp1 inhibitor in wild-type (WT) mice, or Cyp1-null mice (Cyp1a1/1a2-/-, Cyp1b1-/-, and Cyp1a1/1a2/1b1-/-). Low-dose Dox was administered by serial intraperitoneal or intravenous injections, respectively. Expression of Cyp1 isoforms was measured by RT-qPCR, and myocardial tissue was isolated from the left ventricle for RNA sequencing. Cardiac function was evaluated by transthoracic echocardiography. Results: In WT mice, Dox treatment was associated with a decrease in Cyp1a2 and increase in Cyp1b1 expression in the heart and in the liver. Co-treatment of WT mice with Dox and the novel Cyp1 inhibitor YW-130 protected against cardiac dysfunction compared to Dox treatment alone. Cyp1a1/1a2-/- and Cyp1a1/1a2/1b1-/- mice were protected from Dox cardiomyopathy compared to WT mice. Male, but not female, Cyp1b1-/- mice had increased cardiac dysfunction following Dox treatment compared to WT mice. RNA sequencing of myocardial tissue showed upregulation of Fundc1 and downregulation of Ccl21c in Cyp1a1/1a2-/- mice treated with Dox, implicating changes in mitophagy and chemokine-mediated inflammation as possible mechanisms of Cyp1a-mediated cardioprotection. Conclusions: Taken together, this study highlights the potential therapeutic value of Cyp1a inhibition in mitigating anthracycline cardiomyopathy.

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