scholarly journals Periodontal Pathogens and Atherosclerosis: Implications of Inflammation and Oxidative Modification of LDL

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tomoko Kurita-Ochiai ◽  
Masafumi Yamamoto
Keyword(s):  
High Fat Diet ◽  
Oxidative Modification ◽  
Periodontal Pathogen ◽  
Periodontal Pathogens ◽  
Mucosal Vaccination ◽  
Atherosclerotic Lesions ◽  
Causative Agents ◽  
Anti Inflammatory ◽  
Apoe Deficient Mouse

Inflammation is well accepted to play a crucial role in the development of atherosclerotic lesions, and recent studies have demonstrated an association between periodontal disease and cardiovascular disease.Porphyromonas gingivalisandAggregatibacter actinomycetemcomitans, causative agents of destructive chronic inflammation in the periodontium, can accelerate atheroma deposition in animal models. Emerging evidence suggests that vaccination against virulence factors of these pathogens and anti-inflammatory therapy may confer disease resistance. In this review, we focus on the role of inflammatory mechanisms and oxidative modification in the formation and activation of atherosclerotic plaques accelerated byP. gingivalisorA. actinomycetemcomitansin an ApoE-deficient mouse model and high-fat-diet-fed mice. Furthermore, we examine whether mucosal vaccination with a periodontal pathogen or the anti-inflammatory activity of catechins can reduce periodontal pathogen-accelerated atherosclerosis.

scholarly journals Novel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet

2011 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Venkata J Adapala ◽  
Kimberly K Buhman ◽  
Kolapo M Ajuwon
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Anti Inflammatory

Platelet P-selectin facilitates atherosclerotic lesion development

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2661-2666 ◽  
Author(s):  
Peter C. Burger ◽  
Denisa D. Wagner
Keyword(s):  
Atherosclerotic Lesion ◽  
Soluble Form ◽  
Wild Type ◽  
Lesion Development ◽  
Atherosclerotic Lesions ◽  
Lesion Growth ◽  
Microparticle Formation ◽  
Apoe Deficient Mouse ◽  
Atherosclerotic Lesion Development

P-selectin is an adhesion molecule expressed on activated platelets and endothelium. It is known to play an important role in atherosclerosis. P-selectin also circulates in plasma in a soluble form (sP-selectin), which induces procoagulant microparticle formation. We investigated the role of platelet versus endothelial P-selectin in generating sP-selectin and in the formation of atherosclerotic lesions in the apolipoprotein E (apoE)–deficient mouse model. For this we transplanted apoE−/−P-selectin−/− and apoE−/−P-selectin+/+ lethally irradiated mice with bone marrow of either genotype. Seven months after transplantation, we determined from the chimeric animals that the majority of circulating sP-selectin was of endothelial origin. Thus, in atherosclerosis, the procoagulant sP-selectin reflects endothelial rather than platelet activation. We found that endothelial P-selectin was crucial for the promotion of atherosclerotic lesion growth because in its absence only relatively small lesions developed. However, platelet P-selectin also contributed to the lesion development because lesions in wild-type recipients receiving transplants with wild-type platelets were 30% larger than those receiving P-selectin-deficient platelets (P < .008) and were more frequently calcified (80% versus 44%). In comparison with P-selectin wild-type animals, absence of either endothelial or platelet P-selectin inhibited migration of smooth muscle cells into the lesion. Thus, in addition to endothelium, platelets and their P-selectin also actively promote advanced atherosclerotic lesion development.

Abstract 450: Monocytic Glutaredoxin 1 Protects Mice Against Obesity, Hyperglycemia and Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kevin Downs ◽  
Sina Tavakoli ◽  
John D Short ◽  
Huynh N Nguyen ◽  
Reto Asmis
Keyword(s):  
High Fat Diet ◽  
Statistical Significance ◽  
Gene Array ◽  
Metabolic Stress ◽  
Wild Type ◽  
Adipose Tissues ◽  
Atherosclerotic Lesions ◽  
Monocyte Chemotaxis

Overexpression of glutaredoxin 1 (Grx1) protects monocytes from metabolic stress-induced priming, i.e. dysregulation and hypersensitization to chemokines (Ullevig et al. ATVB 2012). To address the role of monocytic Grx1 in mice and in the development of atherogenesis and obesity, we transplanted bone marrow (BM) from either wild-type (WT) or Grx1 -/- donor mice into atherosclerosis-prone LDLR -/- mice and fed these mice a high-fat diet (HFD) for up to 20 weeks. Grx1 Leuko -/- mice showed accelerated weight gain after 9 weeks followed by early onset of hyperglycemia. After 6 weeks on HFD, atherosclerotic lesions were slightly larger in Grx1 Leuko -/- mice than in WT mice, but the differences did not reach statistical significance. However, after 20 weeks, Grx1 Leuko -/- mice showed 36% larger lesions than WT-BM recipients, and monocyte chemotaxis in vivo was increased 1.6-fold. Furthermore, compared to WT-BM recipients, adipose tissues and livers of Grx1 Leuko -/- mice also showed increased macrophage content and elevated tissue inflammation as determined by IHC and qRT-PCR-based gene array. Adipose tissue in particular, showed significant increases in the expression of proinflammatory genes in addition to an increased abundance of proinflammatory “crown-like” structures. In contrast, genes associated with inflammation resolving macrophages were significantly suppressed. Macrophages isolated from Grx1 -/- mice and stimulated with INFγ+TNFα also showed increased expression of pro-inflammatory M1-associated genes, whereas M2-associated genes were suppressed in Grx-1 -/- macrophages activated with IL-4. Furthermore, macrophages from Grx1 -/- mice exposed to metabolic stress also display increased protein S -glutathionylation, enhanced hypersensitization to chemokine, and impaired autophagy compared to macrophages from wild-type mice. Taken together, our data show that loss of monocytic Grx1 worsens monocyte priming in response to HFD-induced metabolic stress and accelerates the infiltration of dysfunctional monocyte-derived macrophages into tissues, such as aorta, liver and adipose tissues. We conclude that monocytic Grx1 is critical for maintaining metabolic homeostasis in mice and protects mice against obesity and atherogenesis.

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

2020 ◽  
Vol 34 (3) ◽  
Author(s):  
Rasha Abdelmawla Ghazala ◽  
Azza El Medney ◽  
Anisa Meleis ◽  
Passant Mohie El dien ◽  
Hend Samir
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Anti Inflammatory

Abstract 347: Water-soluble Components of Sesame Oil Reduces Inflammation and Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Krithika Selvarajan ◽  
Kathryn Burge ◽  
Dmitry Litvinov ◽  
Bhaswati Sengupta ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipids ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Sesame Oil ◽  
Water Soluble ◽  
Gene Analysis ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Anti Inflammatory

Background: Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Non-pharmacological means of treating chronic diseases have gained attention recently. We previously reported that the sesame oil aqueous extract (SOAE) has anti-inflammatory properties both in vitro and in vivo. In this study, we have determined whether SOAE has anti-atherosclerotic properties, and mechanisms by which it might modulate atherosclerosis by identifying genes and inflammatory markers. Methods and results: Low-density lipoprotein receptor knockout (LDLR-/-) female mice were fed with either high fat diet or high fat diet supplemented with SOAE. Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for global cytokine array. RNA was extracted from the liver tissue and the aorta and used for gene analysis. The SOAE-supplemented high fat diet significantly reduced atherosclerotic lesions, plasma cholesterol, and LDL cholesterol levels in LDLR-/- mice. Plasma inflammatory cytokines were reduced, but not significantly, demonstrating an anti-inflammatory property of SOAE. Gene analysis showed that SOAE-supplemented high fat diet reduced the genes involved in inflammation, and induced genes involved in cholesterol metabolism and reverse cholesterol transport. Conclusion: In conclusion, our studies suggest that a SOAE-enriched diet could be an effective non-pharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

scholarly journals Ferryl Hemoglobin and Heme Induce Α1-Microglobulin in Hemorrhaged Atherosclerotic Lesions with Inhibitory Function against Hemoglobin and Lipid Oxidation

2021 ◽  
Vol 22 (13) ◽  
pp. 6668
Author(s):  
Dávid Pethő ◽  
Tamás Gáll ◽  
Zoltán Hendrik ◽  
Annamária Nagy ◽  
Lívia Beke ◽  
...  
Keyword(s):  
Radical Scavenging ◽  
Cell Types ◽  
Oxidative Modification ◽  
Atherosclerotic Plaques ◽  
Aortic Endothelial Cells ◽  
Inhibitory Function ◽  
Atherosclerotic Lesions ◽  
Atheromatous Plaques ◽  
Heme Binding Protein

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy- and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme-catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme-driven oxidative modification of low-density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.

scholarly journals Adiponectin Alleviates Diet-induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration

2021 ◽  
Author(s):  
Jiyoon Ryu ◽  
Jason T. Hadley ◽  
Zhi Li ◽  
Feng Dong ◽  
Huan Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Adaptor Protein ◽  
Macrophage Infiltration ◽  
Hepatic Inflammation ◽  
High Fat ◽  
Mtorc1 Signaling ◽  
Anti Inflammatory

Adiponectin is an adipokine that exerts insulin sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from high fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin sensitizing effects in the APPL2 hepatocyte-specific knockout mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-a-stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. Taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2-mTORC1-MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.

Abstract 265: Platelet C-Type Lectinlike (CLEC)-2 Receptor Plays a Protective Role Against Development of Atherosclerosis in Atherosclerosis-Prone Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marie Lordkipanidze ◽  
Matthew J Harrison ◽  
Steve P Watson ◽  
G E Rainger
Keyword(s):  
High Fat Diet ◽  
Blood Lipid ◽  
Protective Role ◽  
Plaque Burden ◽  
Platelet Glycoprotein ◽  
High Fat ◽  
T Helper 17 ◽  
Platelet Surface ◽  
Atherosclerotic Lesions

Background: Platelets can influence progression of plaque formation by facilitating recruitment of inflammatory cells at the sites of atherosclerotic lesions. A C-type lectin-like receptor, CLEC-2, abundantly expressed on the platelet surface, has been shown to regulate lymphatic development in utero though an interaction with Podoplanin. Interestingly, lymphatic vasculature is increased in ischemic and inflamed hearts, and in cholesterol-rich atherosclerotic lesions. Moreover, Podoplanin expression is up-regulated on inflammatory macrophages and on T-helper 17 cells. However, the role of the Podoplanin - CLEC-2 interaction in atherosclerosis remains unknown. Aim: We sought to investigate the role of CLEC-2 on atherosclerotic development in ApoE-deficient mice. Methods: CreERT.CLEC-2fl/fl x ApoE-/- and litter-matched ApoE-/- mice were treated with tamoxifen at the age of 9 weeks and were put on a high-fat diet for 6 weeks. Animals were killed at the age of 16 weeks, when platelet function assays and atherosclerosis assays were carried out. Results: Expression of CLEC-2 was abolished in tamoxifen-treated CreERT.CLEC-2fl/fl x ApoE-/- mice (n=8), whereas normal levels were seen in ApoE-/- controls (n=10) also treated with tamoxifen. CreERT.CLEC-2fl/fl x ApoE-/- and ApoE-/- mice had similar baseline characteristics, comparable levels of platelet glycoprotein expression (GPIb, GPIIbIIIa and GPVI) and normal platelet responses to platelet agonists (collagen-related peptide, PAR-4 peptide, ADP and arachidonic acid). Blood lipid levels were comparable between CreERT.CLEC-2fl/fl x ApoE-/- and control animals. Atherosclerotic plaque burden was significantly higher in the aortas of CreERT.CLEC-2fl/fl x ApoE-/- mice fed a high-fat diet for 6 weeks compared with their ApoE-/- counterparts. The higher plaque burden was seen consistently throughout the aorta, but reached significance at the level of whole aorta, abdominal aorta, outer curvature and the left subclavian region. This was seen in both male and female animals. Conclusions: The platelet-borne CLEC-2 receptor appears to have a protective role against atherogenesis in atheroprone mice. Further research to investigate the underlying mechanisms is warranted.

Abstract 183: Oxidized LDL Cholesterol Induces Endothelial Dysfunction in the Aorta and Lox-1 Expression in Macrophages

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Anja Leuner ◽  
David M Poitz ◽  
Robert Augustin ◽  
Heike Neubauer ◽  
Coy Brunssen ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
High Fat Diet ◽  
Ldl Cholesterol ◽  
Oxidized Ldl ◽  
High Fat ◽  
Human Macrophages ◽  
Atherosclerotic Lesions ◽  
The Impact

Elevated plasma cholesterol is one of the major risk factors in the development of atherosclerotic lesions. Oxidation of native LDL cholesterol (nLDL) by reactive oxygen species leads to the formation of oxidized LDL (oxLDL). An important receptor for the cellular uptake of oxLDL is the lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1). Lox-1 is highly expressed on macrophages, but also present on arterial endothelial and vascular smooth muscle cells. Especially the uptake by macrophages leads to the formation of foam cells in atherosclerotic lesions. Aim of the present study was to analyze the impact of oxLDL on endothelial function in murine aortas and on Lox-1 expression in human macrophages. In addition, we analyzed the effect of a high-fat diet on vascular function in mice with an endothelial Lox-1 overexpression. First, we incubated aortic rings of wild-type mice for 2 h with 100 μg/mL oxLDL and analyzed the endothelial function using a Mulvany myograph. Compared to basal conditions, oxLDL significantly impaired endothelium-dependent vasodilation. Next, we fed mice with an endothelial overexpression of Lox-1 for 20 weeks a high-fat diet and analyzed the endothelial function in the thoracic aorta. Interestingly, these mice had no impaired endothelium-dependent relaxation after high-fat diet feeding. To get further insight into Lox-1 regulation by oxLDL, we analyzed the impact of oxLDL on Lox-1 expression in human macrophages. Monocytic THP-1 cells were differentiated with phorbol myristate acetate into macrophages and stimulated for 24 h with nLDL or oxLDL. We found a significant induction of Lox-1 mRNA expression after oxLDL incubation, whereas nLDL had no effect. Our data suggest an increased oxLDL uptake in oxLDL-treated macrophages by increased Lox-1 receptor expression. In conclusion, our data support an important role of oxLDL as a proatherosclerotic risk factor by its ability to induce endothelial dysfunction and Lox-1 expression in macrophages. Both processes may be involved in the development of atherosclerotic lesions but the physiological significance and functional role of Lox-1 in contributing to the human disease warrants further investigations.

scholarly journals Chronic NaHS Treatment Is Vasoprotective in High-Fat-Fed ApoE−/−Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Asha Ford ◽  
Mohammad Al-Magableh ◽  
Tracey A. Gaspari ◽  
Joanne L. Hart
Keyword(s):  
High Fat Diet ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Atherosclerotic Lesion ◽  
Vascular Changes ◽  
High Fat ◽  
Superoxide Generation ◽  
Atherosclerotic Lesions ◽  
Atherosclerotic Lesion Development

Hydrogen sulfide is emerging as an important mediator of vascular function that has antioxidant and cytoprotective effects. The aim of this study was to investigate the role of endogenous H2S and the effect of chronic exogenous H2S treatment on vascular function during the progression of atherosclerotic disease. ApoE−/−mice were fed a high-fat diet for 16 weeks and treated with the H2S donor NaHS or the cystathionine-γ-lyase (CSE) inhibitor D,L-propargylglycine (PPG), to inhibit endogenous H2S production for the final 4 weeks. Fat-fed ApoE−/−mice displayed significant aortic atherosclerotic lesions and significantly impaired endothelial function compared to wild-type mice. Importantly, 4 weeks of NaHS treatment significantly reduced vascular dysfunction and inhibited vascular superoxide generation. NaHS treatment significantly reduced the area of aortic atherosclerotic lesions and attenuated systolic blood pressure. Interestingly, inhibiting endogenous, CSE-dependent H2S production with PPG did not exacerbate the deleterious vascular changes seen in the untreated fat-fed ApoE−/−mice. The results indicate NaHS can improve vascular function by reducing vascular superoxide generation and impairing atherosclerotic lesion development. Endogenous H2S production via CSE is insufficient to counter the atherogenic effects seen in this model; however exogenous H2S treatment has a significant vasoprotective effect.

Sign in / Sign up

Export Citation Format

Share Document