Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases

Altara, Raffaele; Manca, Marco; Brandão, Rita D.; Zeidan, Asad; Booz, George W.; Zouein, Fouad A.

doi:10.1042/cs20150666

Cited by 71 publications

(72 citation statements)

References 153 publications

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“…Using in silico target prediction analysis and luciferase reporter assays, we observed that PDLIM1 was the target gene most significantly upregulated in the BMDMs of miR-150 / ApoE / mice and that PDLIM1 luciferase activity was enhanced by miR-150 inhibitor transfection; however, these changes were prevented by the mutation of the predicted binding sites within the PDLIM1 3′UTR. Moreover, we noted that CXCL3 and CXCL2, which play important roles in macrophage recruitment and plaque progression (39)(40)(41), were downregulated in the BMDMs of miR-150 / ApoE / mice. In a previous study, PDLIM1 decreased phosphorylated p65 expression and attenuated pro-inflammatory cytokine/chemokine secretions (42).…”

Section: Discussionmentioning

confidence: 86%

Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

Gong

Cheng

Wang

et al. 2018

Journal of Lipid Research

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Atherosclerosis is considered to be a chronic inflammatory disease that can lead to severe clinically important cardiovascular events. miR-150 is a small noncoding RNA that significantly enhances inflammatory responses by upregulating endothelial cell proliferation and migration, as well as intravascular environmental homeostasis. However, the exact role of miR-150 in atherosclerosis remains unknown. Here, we investigated the effect of miR-150 deficiency on atherosclerosis development. Using double-knockout (miR-150 and ApoE) mice, we measured atherosclerotic lesion size and stability. Meanwhile, we conducted in vivo bone marrow transplantation to identify cellular-level components of the inflammatory response. Compared with mice deficient only in ApoE, the double-knockout mice had significantly smaller atherosclerotic lesions and displayed an attenuated inflammatory response. Moreover, miR-150 ablation promoted plaque stabilization via increases in smooth muscle cell and collagen content and decreased macrophage infiltration and lipid accumulation. The in vitro experiments indicated that an inflammatory response with miR-150 deficiency in atherosclerosis results directly from upregulated expression of the cytoskeletal protein, PDZ and LIM domain 1 (PDLIM1), in macrophages. More importantly, the decreases in phosphorylated p65 expression and inflammatory cytokine secretion induced by miR-150 ablation were reversed by PDLIM1 knockdown. These findings suggest that miR-150 is a promising target for the management of atherosclerosis.

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Section: Discussionmentioning

confidence: 86%

Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

Gong

Cheng

Wang

et al. 2018

Journal of Lipid Research

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“…Emerging evidence has shown that chemokines play a critical role in early myocardial dysfunction and disease progression following MI by regulating infarct angiogenesis, leukocyte infiltration and fibrous tissue deposition252627. The infarct size can be reduced and cardiomyocyte injury can be prevented by targeting chemokine-mediated inflammation in the post-MI heart282930313233.…”

Section: Discussionmentioning

confidence: 99%

Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction

Huang

Wang

et al. 2016

Sci Rep

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CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

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“…CCL26 was unique in that its level was significantly diminished before TX and saw a significant elevation in a large number of patients after transplant to the extent that in all post-TX patients, CCL26 was uniquely elevated above the upper pre-TX level. This central finding suggests that there may be a biological relevance to this molecule in transplant immunobiology [40, 41]. Interestingly, this chemokine uses-receptor that is present on eosinophils, basophils, T helper 2, monocytes, dentritic cells, plasma cells and natural killer cells.…”

Section: Discussionmentioning

confidence: 99%

Circulating chemokine ligand levels before and after successful kidney transplantation

et al. 2016

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BackgroundChemokine ligands (CCLs) play a pivotal role in tissue injury before and after kidney transplantation. Meanwhile, transplantation improves patient’s survival and diminishes morbidity. It is hypothesized, then, that kidney transplantation diminishes pre-transplant (pre-TX) levels of circulating inflammatory CCLs. This retrospective study compared circulating levels and profiles of CCLs before transplantation (pre-TX) and after transplantation (post-TX).MethodsNineteen CCLs (1, 2, 3, 4, 5, 8, 11, 13, 15, 17, 21, 24, 26, 27, CXCL 5, 8, 10, 12 and 13) were measured in 47 stable post-TX recipients, and their stored pre-TX plasma was analyzed by multiplexed fluorescent bead-based immunoassay. Twenty normal controls were included for comparisons. Normalized data was presented as mean ± SD and non-normalized data as median (5–95 % CI). Significance was measured at p < 0.01. Arbitrary upper and lower margins for each CCL at the 95 % CI or 2SD levels in each group were chosen to calculate the percentile of patients in the other group who exceeded these limits. Significant CCL levels present in more than 75 % of patients in a group that exceeded the arbitrary upper or lower set margins in the other two groups were labeled as preferentially characteristic for the respective group.ResultsMore than 75 % of pre- and post-TX patients had levels that exceeded the upper control for CCL1, 11, 15 and CCL15, CCL26 and CXCL13 levels, respectively. More than 75 % of pre- and post-TX patients exceeded the lower control for CCL3, 21, and CCL5 limits, respectively. More than 75 % of post-TX patients demonstrated elevated levels of CCL2, 3, 21, 26 and CXCL13 above the upper pre-TX cut offs. Meanwhile, more than 75 % of post-TX patients exceeded the lower pre-TX levels for CCL1, 4, 5, 8, 13, 15, 17, 24 and CXCL8 and10. Pre-TX was preferentially characterized by elevated CCL1 and 15 and diminished CCL3 and 21. Post-TX was preferentially characterized by elevated CCL26 and CXCL13 and diminished CCL4 and 5.ConclusionEnd stage kidney disease is associated with enhanced circulating inflammatory chemokine levels. Stable kidney transplantation is associated with 1) lowered burden of circulating inflammatory chemokine levels and, 2) elevation in the pro T-helper2 chemokine, CCL26 and the homeostatic CXCL13.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-016-0141-4) contains supplementary material, which is available to authorized users.

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Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases

Cited by 71 publications

References 153 publications

Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction

Circulating chemokine ligand levels before and after successful kidney transplantation

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