Abstract
BackgroundMyocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage response are recent research hotspots. Hence, we attempted to examine the role of C-X-C motif chemokine 16 (CXCL16) as a potential candidate in MI.MethodsHuman cardiomyocytes were treated with hypoxia/reoxygenation (H/R) to establish an in vitro cell model. GEO database provided the clinical data of MI patients and GSEA verified the relationship of chemokine and MI. CCK-8 and flow cytometry analyses were used to measure cell viability and apoptosis. Bioinformatics analysis and luciferase reporter assay were conducted to determine the correlation between CXCL16 and miR-545. qRT-PCR and western blot assays were performed to investigate the expression level of the indicated genes. The activity of lactate dehydrogenase (LDH) and the levels of TNF-α, IL-6, IL-1β, and IL-10 were explored using ELISA assay.ResultsCXCL16 was increased in MI. CXCL16 knockdown can reverse the inhibitory effect of H/R treatment on cell viability, while overexpression of CXCL16 showed the opposite trend. MiR-545 directly targeted CXCL16 and negatively regulated CXCL16 levels. MiR-545 promoted cell proliferation and inhibited apoptosis in the MI cell model, which attenuated the CXCL16-induced injury on cardiomyocytes.ConclusionThese findings demonstrated that CXCL16 aggravated MI damage through being directly targeted by miR-545 and mediating inflammatory responses, thereby providing potential therapeutic targets for MI therapy.
Highlights
Myocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world
CXCL16 expresses at higher levels in MI and human neonatal cardiomyocytes in response to H/R treatment The appearance of chemokines is the main feature of inflammatory response after myocardial injury [5]
In order to investigate the relationship of chemokine and MI, Gene Set Enrichment Analysis (GSEA) was implemented based on the KEGG gene set of MSigDB database and revealed that chemokines were positively correlated with the MI process
Summary
Myocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage response are recent research hotspots. We attempted to examine the role of C-X-C motif chemokine 16 (CXCL16) as a potential candidate in MI. Myocardial infarction (MI), induced by coronary artery occlusion, is one of the leading causes of cardiac eventrelated mortality worldwide and results in ischemic death of cardiac tissue [1]. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage responses emerge as hotspots in recent years. In a soluble form, CXCL16 has been identified as an independent factor of cardiovascular death and morbidity in acute coronary syndromes [13]. The biological functions of soluble CXCL16 in MI and the underlying mechanism have not been fully illustrated
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