scholarly journals ICAM-1: Contribution to Vascular Inflammation and Early Atherosclerosis

Author(s):  
Sabine I. ◽  
Charlotte Lawso
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2178-2178
Author(s):  
Chintan Gandhi ◽  
Steven R. Lentz ◽  
Anil K Chauhan

Abstract Abstract 2178 Background and objective: The metalloprotease ADAMTS13 prevents spontaneous thrombosis in the microvasculature by cleaving hyperactive ultra large von Willebrand factor (ULVWF) multimers into smaller and less active forms. Recently, we and others have demonstrated that ADAMTS13-deficiency aggravates vascular inflammation and early atherosclerosis in apolipoprotein E-deficient (ApoE−/−) mice fed a high-fat Western diet. Although VWF is the only known substrate for ADAMTS13, it is not known if the effects of ADAMTS13 on vascular inflammation and atherosclerosis are mediated through its proteolytic effects on VWF or possibly another ADAMTS13 substrate. In this study, we determined whether the exacerbated atherosclerosis observed in the Adamts13−/−/ApoE−/− mice is dependent or independent of VWF. Model and methods: ApoE−/−, Adamts13−/−/ApoE−/−, Adamts13−/−/Vwf−/−/ApoE−/− and Vwf−/−/ApoE−/− male mice were fed a high-fat Western diet (20% fat, 0.2% cholesterol) beginning at 6 weeks of age until they were sacrificed at 4 months. We compared the extent of atherosclerosis in the cross section area of the aortic sinus using the VerHoeffs/Van Gieson stain. Inflammatory cells (neutrophils and macrophages) in the aortic lesions were quantitated by immunohistochemistry. Results: Similar to previous published reports by us and others, we found that the mean lesion area in the aortic sinus of the Adamts13−/−/ApoE−/− mice were significantly larger (mean ± SEM: 26.6 % ± 1.9 %, P<0.01) compared with ApoE−/− mice (mean ± SEM: 20.4 % ± 1.5 %). Next, we quantitated macrophage and neutrophil infiltration into lesions in the aortic sinus by immunohistochemistry. We observed significantly increased macrophages (mac-3 positive) and neutrophils (Ly6 B.2 positive) recruitment in the aortic sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice. The mean lesion area in the aortic sinus of Adamts13−/−/Vwf−/−/ApoE−/− mice (mean ± SEM: 15.2 % ± 1.5 %) were similar to Vwf−/−/ApoE−/− mice (mean ± SEM: 15.6 % ± 0.9 %), suggesting that the accelerated atherosclerosis observed in ADAMTS13-deficient mice is VWF-dependent. Finally, macrophages and neutrophils recruitment in the aortic sinus of Adamts13−/−/Vwf−/−/ApoE−/− mice were similar to Vwf−/−/ApoE−/− mice, suggesting that increased vascular inflammation observed in ADAMTS13-deficient mice is also VWF-dependent. Total cholesterol and triglyceride levels were similar among groups fed a high-fat Western diet. Conclusion: These findings reveal that VWF-deficiency abrogates accelerated early atherosclerosis in ADAMTS13-deficient mice, suggesting that VWF the only relevant substrate for ADAMTS13 in murine atherosclerosis. Disclosures: Lentz: Novo Nordisk A/S: Consultancy, Investigator Other.


2018 ◽  
Vol 9 (4) ◽  
pp. 2090-2101 ◽  
Author(s):  
Su Jeong Ha ◽  
Jangho Lee ◽  
Kyung-Mo Song ◽  
Young Ho Kim ◽  
Nam Hyouck Lee ◽  
...  

This study evaluated the use of ultrasonication to extract Lespedeza cuneata as a potential nutraceutical for preventing vascular inflammation.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Maria Chiara Maiuri ◽  
Gianluca Grassia ◽  
Andrew M. Platt ◽  
Rosa Carnuccio ◽  
Armando Ialenti ◽  
...  

Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yushuang Chai ◽  
Zhen Yin ◽  
Qinghong Fan ◽  
Zhe Zhang ◽  
Kaihe Ye ◽  
...  

Atherosclerosis (AS) is the primary cause of cardiocerebrovascular disease, and inflammation is responsible for the initiation of its pathogenesis. Therefore, targeting inflammatory pathways to prevent AS progression is an ideal strategy. Angong Niuhuang pill (ANP) is a well-known traditional Chinese medicine and has been widely used for thousands of years to treat central nervous system and cardiovascular diseases. In this study, we investigated the role of ANP in reducing inflammation during early AS, using a high-fat diet-induced ApoE−/− mouse model of AS. Compared to those with simvastatin, ANP had no significant effect on serum triglyceride, low-density lipoprotein, and high-density lipoprotein levels. However, it effectively inhibited splenic and vascular inflammation. This agent also reduced the Th17/CD4+T ratio and mRNA expression of IL-6 and increased the Treg/CD4+T ratio and mRNA expression of TGF-β1. Thus, ANP restored Th17/Treg homeostasis in the spleen. It also regulated pro- and anti-inflammatory cytokine expression in the aorta in a similar manner. Further, it downregulated the expression of chemokine receptors (CCR2, CXCR3), their ligands (MCP-1, MCP-2, and MCP-3), and cell adhesion molecules (VCAM-1, ICAM-1) in arterial vessels. These results indicate that ANP can ameliorate the development of early AS, mainly by reducing inflammation instead of acting as an antihyperlipidemic drug.


Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2385-2391 ◽  
Author(s):  
Chintan Gandhi ◽  
Mohammad Moshahid Khan ◽  
Steven R. Lentz ◽  
Anil K. Chauhan

Abstract ADAMTS13, a metalloprotease, plays a pivotal role in preventing spontaneous microvascular thrombosis by cleaving hyperactive ultra large von Willebrand factor multimers into smaller, less active multimers. Reduced ADAMTS13 activity in plasma has been described in many diseases associated with systemic inflammation. It remains uncertain, however, whether ADAMTS13 contributes to disease pathogenesis or rather simply serves as an inflammation-associated marker. We hypothesized that, by decreasing vascular inflammation, ADAMTS13 reduces the development of early atherosclerotic plaques. Using intravital fluorescence microscopy, we observed excessive leukocyte adhesion and accelerated atherosclerotic plaque formation at the carotid sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice fed a high-fat Western diet. At 4 months of age, there was a significant increase in atherosclerosis in the aorta and aortic sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice. Interestingly, we detected a 2-fold increase in macrophage recruitment to the atherosclerotic plaque of the Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice, suggesting that the atherosclerotic lesions in these mice were not only larger but also more inflammatory. These findings reveal a new functional role for the antithrombotic enzyme ADAMTS13 in reducing excessive vascular inflammation and plaque formation during early atherosclerosis.


2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.


2016 ◽  
Vol 5 (2) ◽  
pp. 83-91
Author(s):  
Miftafu Darussalam ◽  
Dwi Kartika Rukmi

Background: Uric acid is a final product or a waste that is resulted from the metabolism of purines. A high level of uric acid (hyperuricemia) will cause several health problems, such as vascular inflammation, smooth muscle proliferation, and vascular lesion in kidneys. The syzygium polyanthum leaves contain bioactive substances that may affect the level of uric acid in blood. Objective: This study aimed to determine the influence of boiled water of syzygium polyanthum leaves to the changes of uric acid levels in the target area of Puskesmas Pandak 1 Bantul. Methods: This study employed pre- and post-test without control group design. The population consisted of all patients with hyperuricemia in the target area of Puskesmas Pandak 1 Bantul. Sample was selected with a concecutive sampling, gaining a total number of 24 respondents. Data were analyzed with the Wilcoxon test. The dose of boiled water of syzygium polyanthum leaves intake was 0.36g/ KgBW, once a day for 14 days. Result: This research showed that the boiled water of syzygium polyanthum leaves decreased hyperuricemia (uric acid levels), along with the significancy value of 0.009 (p <0.05). At the pre-test time, the average level of uric acid reached 7.279 mg/dl, and after the treatment, it decreased to 6.76 mg/dl. Conclusion: This study has established evidence that the boiled water of syzygium polyanthum leaves is able to decrease hyperuricemia (uric acid level in blood). Keywords: syzygium polyanthum, boiled water of syzygium polyanthum leaves, hyperuricemia


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