scholarly journals Galectin-3 Gene Inactivation Reduces Atherosclerotic Lesions and Adventitial Inflammation in ApoE-Deficient Mice

2008 ◽  
Vol 172 (1) ◽  
pp. 247-255 ◽  
Author(s):  
Maurice Nachtigal ◽  
Abdul Ghaffar ◽  
Eugene P. Mayer
Keyword(s):  
Gene Inactivation ◽  
Atherosclerotic Lesions ◽  
Galectin 3 ◽  
Deficient Mice

scholarly journals Modified citrus pectin inhibits galectin-3 function to reduce atherosclerotic lesions in apoE-deficient mice

2017 ◽  
Vol 16 (1) ◽  
pp. 647-653 ◽  
Author(s):  
Yonggang Lu ◽  
Mingming Zhang ◽  
Pei Zhao ◽  
Min Jia ◽  
Bing Liu ◽  
...  
Keyword(s):  
Citrus Pectin ◽  
Atherosclerotic Lesions ◽  
Galectin 3 ◽  
Deficient Mice

Macrophage P53 controls foam cell death in atherosclerotic lesions of apolipoprotein E deficient mice

2006 ◽  
Vol 45 (3) ◽  
pp. e4
Author(s):  
Marion J.J. Gijbels ◽  
Lianne S.M. Boesten ◽  
A. Suzanne M. Zadelaar ◽  
Aart G. Jochemsen ◽  
Bob van de Water ◽  
...  
Keyword(s):  
Cell Death ◽  
Apolipoprotein E ◽  
Foam Cell ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Abstract 252: Interleukin-27 Signaling Regulates Myeloid Cells Activation in Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Iuliia Peshkova ◽  
Aliia Fatkhullina ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Antigen Presenting Cells ◽  
Atherosclerotic Lesions ◽  
Mediators Of Inflammation ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a lipid-driven inflammatory disease characterized by the progressive plaque growth in the vessels. Cytokines are important mediators of inflammation and atherosclerosis. While pro-inflammatory cytokines were extensively investigated, little is known about the role of anti-inflammatory cytokines as to their ability to control vascular inflammation. We tested whether immunoregulatory IL-27R signaling is important to control inflammation in mouse models of atherosclerosis. We found that atherosclerosis-prone mice with hematopoietic deficiency of IL-27R ( Ldlr -/- mice reconstituted with bone marrow from Il27ra -/- ) or global deficiency ( Il27ra -/- x Apoe -/- ) developed significantly larger atherosclerotic lesions compared to controls. Atherosclerotic lesions in IL-27R deficient mice contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in atherosclerotic aortas. Using two-photon microscopy, we found enhanced interactions between antigen presenting cells and T cells in the aortas of IL-27R deficient mice accompanied by enhanced CD4 T cell proliferation. Moreover, macrophages in Il27ra -/- aortas also demonstrated enhanced ability to produce pro-inflammatory cytokines, including IL-1. The blockade of IL-1R signaling, however, strongly suppressed atherosclerosis progression in IL-27R deficient but not control mice, suggesting an important role of IL-27 in the regulation of IL-1 production in atherosclerosis. Overall, our data demonstrate that IL-27R signaling in atherosclerosis is required to control function of antigen presenting cells modulating subsequent T cell activation in the aortas. Moreover, it controls macrophage activation and pro-inflammatory myeloid cell-derived cytokine production. These mechanisms altogether curb pathogenic T cell lineage differentiation and, thus, atherosclerosis, suggesting potent anti-atherogenic role of IL-27.

scholarly journals Deletion of bone marrow myeloperoxidase attenuates chronic kidney disease accelerated atherosclerosis

2020 ◽  
pp. jbc.RA120.014095
Author(s):  
Anna V Mathew ◽  
Lixia Zeng ◽  
Kevin B Atkins ◽  
Kiana N Sadri ◽  
Jaeman Byun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Bone Marrow Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Cholesterol Diet ◽  
Aortic Plaque ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Increased myeloperoxidase (MPO) expression and activity are associated with atherosclerotic disease in patients with chronic kidney disease (CKD). However, the causal relationship between MPO and the development and progression of atherosclerosis in patients with CKD is unknown. Eight-week-old male low-density-lipoprotein-receptor–deficient mice were subjected to 5/6 nephrectomy, irradiated, and transplanted with bone marrow from MPO-deficient mice to induce bone marrow MPO deletion (CKD-bMPOKO) or bone marrow from WT mice as a control to maintain preserved bone marrow MPO(CKD-bMPOWT). The mice were maintained on a high-fat/high-cholesterol diet for 16 weeks. As anticipated, both groups of mice exhibited all features of moderate CKD, including elevated plasma creatinine, lower hematocrit, and increased intact parathyroid hormone but did not demonstrate any differences between the groups. Irradiation and bone marrow transplantation did not further affect body weight, blood pressure, creatinine, or hematocrit in either group. The absence of MPO expression in the bone marrow and atherosclerotic lesions of the aorta in the CKD-bMPOKO mice was confirmed by immunoblot and immunohistochemistry, respectively. Decreased MPO activity was substantiated by the absence of 3-chlorotyrosine, a specific byproduct of MPO, in aortic atherosclerotic lesions as determined by both immunohistochemistry and highly sensitive LC-MS. Quantification of the aortic lesional area stained with oil red O revealed that CKD-bMPOKO mice had significantly decreased aortic plaque area as compared with CKD-bMPOWT mice. This study demonstrates the reduction of atherosclerosis in CKD mice with the deletion of MPO in bone marrow cells, strongly implicating bone marrow-derived MPO in the pathogenesis of CKD atherosclerosis.

Pharmacological inhibition of C-C chemokine receptor 4 aggravates atherosclerosis through prevention of regulatory T cell recruitment to the lesions

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Amin ◽  
N Sasaki ◽  
S Horibe ◽  
S Kawauchi ◽  
K Hirata ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Chemokine Receptor ◽  
Flow Cytometric Analysis ◽  
Atherosclerotic Lesion ◽  
Plaque Formation ◽  
Atherosclerotic Lesions ◽  
Sites Of Action ◽  
Chemokine Receptor 4 ◽  
Deficient Mice

Abstract Background Regulatory T cells (Tregs) are demonstrated to play a protective role in the development of atherosclerosis. However, their sites of action in atherosclerosis remain unclear. Although C-C chemokine receptor 4 (CCR4) has been shown to contribute to the accumulation of Tregs in inflamed tissues and prevention of experimental autoimmune diseases, the role of CCR4 in Treg migration to atherosclerotic lesions and suppression of plaque formation remains unknown. Methods and results We intraperitoneally injected 8-week-old apolipoprotein E–deficient mice fed a normal diet with vehicle (n=9) or a 4-μg dose of a CCR4 antagonist (n=10) 3 times weekly for 8 weeks and evaluated atherosclerotic lesions at 16 weeks old. Administration of the CCR4 antagonist significantly aggravated atherosclerotic plaque formation (aortic sinus plaque area: 2.91±0.87×104 μm2 versus 5.41±0.98×104 μm2 in control vehicle-treated and CCR4 antagonist-treated mice, respectively; P<0.05), associated with increased accumulation of macrophages and CD4+T cells in the plaques. Flow cytometric analysis revealed a decrease in Foxp3+ Tregs in the para-aortic lymph nodes and thoracoabdominal aortas of CCR4 antagonist-treated mice, along with a tendency toward increase in CD44highCD62Lloweffector T cells in para-aortic lymph nodes, indicating CCR4-dependent migration of Tregs to atherosclerotic lesions and their possible atheroprotective role. We observed no changes in splenic Foxp3+ Tregs and effector T cells following CCR4 antagonist treatment. We also investigated the effect of CCR4 blockade on advanced atherosclerosis using LDL receptor–deficient mice fed a high-cholesterol diet. Although 8-week treatment with the CCR4 antagonist led to a decrease in Foxp3+ Tregs in the atherosclerotic lesions, atherosclerotic lesion formation was not significantly affected, suggesting that CCR4-dependent Treg accumulation in atherosclerotic lesions is not critical for prevention of advanced atherosclerosis. Conclusions Our findings indicate an important role for CCR4 in promotion of Treg recruitment into atherosclerotic lesions and subsequent prevention of early atherosclerosis and suggest CCR4 as a novel therapeutic target for atherosclerosis. Funding Acknowledgement Type of funding source: None

Deficiency of the purinergic receptor P2X4 limits atherosclerosis in mice

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Koenig ◽  
A Peikert ◽  
J Merz ◽  
K Rofa ◽  
I Schaefer ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Aortic Root ◽  
Peripheral Blood ◽  
Leukocyte Recruitment ◽  
Funding Source ◽  
P2x4 Receptor ◽  
Atherosclerotic Lesions ◽  
Anti Inflammatory ◽  
Deficient Mice ◽  
Research Grant

Abstract Introduction Extracellular nucleotides like ATP promote inflammation as danger signals in various chronic diseases via purinergic receptors. In our previous work we identified P2X4 expression in murine atherosclerotic lesions. Therefore, we hypothesized a contribution of the ATP-P2X4 axis to vascular inflammation in atherosclerosis. Methods To investigate the functional role of P2X4 in atherogenesis, wild-type LDL-receptor deficient mice (LDLR−/−) and P2X4-deficient LDLR−/− mice (P2X4−/−LDLR−/−) were fed a high cholesterol diet for 16 weeks. Plaque progression in aortic arches was monitored by echography at intervals of 4 weeks, and leukocyte subsets in blood samples were analysed by flow cytometry. Atherosclerotic lesions were then assessed histologically in aortic root, arch, and abdominal aorta. In order to assess leukocyte recruitment, intravital microscopy was performed after injection of ATP in P2X4−/− or wildtype mice (WT). Regarding transferability to human disease, atherosclerotic plaque from carotid endarterectomy has been stained immunohistochemically for P2X4-receptor expression. Results After 16 weeks, P2X4-deficient mice showed significantly reduced atherosclerotic lesions in the aortic root (n=40, LDLR−/−: 0.47 mm2, P2X4−/−LDLR−/−: 0.39 mm2, p=0.04). Ly6C- monocyte count in peripheral blood was higher in P2X4−/−LDLR−/− (n=32, LDLR−/−: 241/μl, P2X4−/−LDLR−/−: 542/μl, p=0.0088), shifting the balance to a more anti-inflammatory subset. Memory-cell generation of CD4-T-cells is significantly higher in knockout-mice, suggesting an involvement of T-helper cells (n=25, LDLR−/−: 27%, P2X4−/−LDLR−/−: 46%, p=0.0003). Peritoneally injected ATP induced leukocyte rolling in WT, but not in P2X4-deficient mice. In human carotid arteries, atherosclerotic plaque shows higher staining for P2X4−/− receptor than not diseased areas. Conclusion P2X4-deficiency enhances anti-inflammatory leukocytes in peripheral blood and reduces atherosclerosis. Therefore, blocking the ATP-P2X4 axis may prevent leukocyte recruitment to atherosclerotic lesions and could present a potential new target for anti-atherogenic therapy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by a research grant of the German Research Foundation (DFG) to Peter Stachon. Sebastian König was supported by a research grant of the German Cardiac Society (DGK)

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