scholarly journals Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

2021 ◽  
Author(s):  
Tomohiro Komatsu ◽  
Makoto Ayaori ◽  
Harumi Uto-Kondo ◽  
Katsumi Hayashi ◽  
Katsumi Tamura ◽  
...  
Keyword(s):  
Atherosclerotic Plaques ◽  
Plaque Inflammation

scholarly journals Systemic delivery of rAAV9‐IκBα stabilized atherosclerotic plaques and attenuated intra-plaque inflammation by inhibiting nuclear factor-κB activation in apolipoprotein E–deficient mice

2021 ◽  
Author(s):  
Qing-Jie Chen ◽  
Fen Liu ◽  
Xue-Mei Wang ◽  
Jia Xie ◽  
Long Zhao ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Vulnerability Index ◽  
The Body ◽  
Atherosclerotic Plaques ◽  
Nuclear Factor ◽  
Systemic Delivery ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Inflammation

Abstract Background: The activated nuclear factor (NF)-κB pathway in atherosclerotic plaques promotes the progression of atherosclerosis. Targeting of plaque NF-κB may provide a novel strategy for limiting chronic inflammation. This study was conducted to examine the effect of NF-κB inhibition by using recombinant adeno-associated virus 9 (AAV9) to deliver IκBα (AAV9‐IκBα) which can be overexpressed to influence atherosclerosis.Methods and Results: Systemic delivery of AAV9‐IκBα resulted in ~2-fold overexpression of IκBα protein in the atherosclerotic plaques of apolipoprotein E-/- mice fed a high-fat diet. AAV9‐IκBα delivery did not affect the body weight or lipid deposition and plaque size in the mice. During plaque formation, overexpression of IκBα suppressed intra-plaque macrophage infiltration, inhibited the expression of pro-inflammatory genes including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α and matrix metalloproteinase, enhanced the contents of collagen and vascular smooth muscle cells, and decreased the plaque vulnerability index by inhibiting the phosphorylation of NF-κB subunit p65 and its nuclear translocation. Conclusions: Systemic delivery of AAV9-IκBα promotes plaque stability by inhibiting NF-κB activation and suppressing intra-plaque inflammation, suggesting that inhibition of the NF-κB pathway in atherosclerotic plaques is a promising approach for treating atherosclerosis.

scholarly journals Effective atherosclerotic plaque inflammation inhibition with targeted drug delivery by hyaluronan conjugated atorvastatin nanoparticles

Nanoscale ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 9541-9556 ◽  
Author(s):  
Seyedmehdi Hossaini Nasr ◽  
Zahra Rashidijahanabad ◽  
Sherif Ramadan ◽  
Nate Kauffman ◽  
Narayanan Parameswaran ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Atherosclerotic Plaque ◽  
Targeted Drug Delivery ◽  
Atherosclerotic Plaques ◽  
Plaque Inflammation ◽  
Targeted Drug

Atherosclerosis is associated with inflammation in the arteries. Hyaluronan atorvastatin nanoparticle conjugate could target CD44 overexpressed in atherosclerotic plaques and significantly reduce plaque associated inflammation.

scholarly journals The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Tiewei Li ◽  
Xiaojuan Li ◽  
Yichuan Feng ◽  
Geng Dong ◽  
Yuewu Wang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Atherosclerotic Plaque ◽  
Predictive Biomarker ◽  
Matrix Metalloproteinase 9 ◽  
Atherosclerotic Plaques ◽  
Plaque Instability ◽  
Cerebrovascular Events ◽  
Plaque Inflammation ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) belongs to the MMP family and has been widely investigated. Excessive MMP-9 expression can enhance extracellular matrix degradation and promote plaque instability. Studies have demonstrated that MMP-9 levels are higher in vulnerable plaques than in stable plaques. Additionally, several human studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and a risk factor for future adverse cardiovascular and cerebrovascular events. MMP-9 deficiency or blocking MMP-9 expression can inhibit plaque inflammation and prevent atherosclerotic plaque instability. All of these results suggest that MMP-9 may be a useful predictive biomarker for vulnerable atherosclerotic plaques, as well as a therapeutic target for preventing atherosclerotic plaque instability. In this review, we describe the structure, function, and regulation of MMP-9. We also discuss the role of MMP-9 in predicting and preventing atherosclerotic plaque instability.

scholarly journals miR-33 Silencing Reprograms the Immune Cell Landscape in Atherosclerotic Plaques

2021 ◽  
Author(s):  
Milessa Silva Afonso ◽  
Monika Sharma ◽  
Martin Paul Schlegel ◽  
Coen van Solingen ◽  
Graeme J Koelwyn ◽  
...  
Keyword(s):  
T Cells ◽  
Lipid Metabolism ◽  
Energy Homeostasis ◽  
Target Genes ◽  
Immune Cell ◽  
Dynamic Balance ◽  
T Cell Subsets ◽  
Plaque Burden ◽  
Atherosclerotic Plaques ◽  
Plaque Inflammation

Rationale: MicroRNA-33 post-transcriptionally represses genes involved in lipid metabolism and energy homeostasis. Targeted inhibition of miR-33 increases plasma HDL cholesterol and promotes atherosclerosis regression, in part, by enhancing reverse cholesterol transport and dampening plaque inflammation. However, how miR-33 reshapes the immune microenvironment of plaques remains poorly understood. Objective: To define how miR-33 inhibition alters the dynamic balance and transcriptional landscape of immune cells in atherosclerotic plaques. Methods and Results: We used single cell RNA-sequencing of aortic CD45 + cells, combined with immunohistologic, morphometric and flow cytometric analyses to define the changes in plaque immune cell composition, gene expression and function following miR-33 inhibition. We report that anti-miR-33 treatment of Ldlr -/- mice with advanced atherosclerosis reduced plaque burden and altered the plaque immune cell landscape by shifting the balance of pro- and anti-atherosclerotic macrophage and T cell subsets. By quantifying the kinetic processes that determine plaque macrophage burden, we found that anti-miR-33 reduced levels of circulating monocytes and splenic myeloid progenitors, decreased macrophage proliferation and retention, and promoted macrophage attrition by apoptosis and efferocytotic clearance. scRNA-sequencing of aortic arch plaques showed that anti-miR-33 reduced the frequency of MHCIIhi "inflammatory" and Trem2hi "metabolic" macrophages, but not tissue resident macrophages. Furthermore, anti-miR-33 led to derepression of distinct miR-33 target genes in the different macrophage subsets: in resident and Trem2hi macrophages, anti-miR-33 relieved repression of miR-33 target genes involved in lipid metabolism (e.g., Abca1, Ncoa1, Ncoa2, Crot), whereas in MHCIIhi macrophages, anti-miR-33 upregulated target genes involved in chromatin remodeling and transcriptional regulation. Anti-miR-33 also reduced the accumulation of aortic CD8+ T cells and CD4+ Th1 cells, and increased levels of FoxP3+ regulatory T cells in plaques, consistent with an immune-dampening effect on plaque inflammation. Conclusions: Our results provide insight into the immune mechanisms and cellular players that execute anti-miR-33's atheroprotective actions in the plaque.

scholarly journals Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

2015 ◽  
Vol 1 (3) ◽  
pp. e1400223 ◽  
Author(s):  
Jun Tang ◽  
Mark E. Lobatto ◽  
Laurien Hassing ◽  
Susanne van der Staay ◽  
Sarian M. van Rijs ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Statin Treatment ◽  
Atherosclerotic Plaques ◽  
Rapid Reduction ◽  
Therapeutic Benefits ◽  
Plaque Inflammation ◽  
Deficient Mice ◽  
Plaque Macrophage ◽  
Macrophage Accumulation

Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.

Abstract 142: Rac2 Modulates Macrophage IL-1β Production, Atherosclerotic Plaque Inflammation, and Calcific Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Nicolle M Ceneri ◽  
Bryan D Young ◽  
Timur O Yarovinsky ◽  
Mehran Sadeghi ◽  
Jeffrey R Bender ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Near Infrared ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Regulatory Elements ◽  
Aortic Tissue ◽  
Atherosclerotic Plaques ◽  
Pathologic Finding ◽  
Plaque Inflammation ◽  
Aortic Plaques

Ischemic heart disease caused by atherosclerosis is the leading cause of morbidity and mortality in the world. Calcification of atherosclerotic plaques is a well-described pathologic finding that has predictive value in terms of atherosclerotic burden, cardiovascular event risk, and mortality. Inflammation is critical to atherogenesis, but inflammatory mechanisms that drive atherosclerotic calcification are minimally understood. The Rho/Rac family of low molecular weight GTPases regulates the activation, recruitment, and differentiation of monocytes. Racs compete for similar regulatory elements, indicating that targeted modulation of specific family members may influence the role of other members in biologic processes. The hypothesis is that Rac2 can modulate atherosclerotic plaque inflammation and calcium composition via consequent effects on the activation of Rac1. Rac2 gene deletion results in elevated activation (GTP-binding) of Rac1 in macrophages. Increased activation of Rac1 is associated with higher macrophage IL-1β production in response to LPS-coupled cholesterol crystal exposure. In fact, macrophage IL-1β production is dependent on Rac1. When subjected to a high fat diet for 14 weeks, Rac2 -/-ApoE -/- mice demonstrate similar weight gain, serum cholesterol levels, circulating inflammatory monocyte levels, and aortic atherosclerotic lipid burden relative to Rac2 +/+ApoE -/- mice. Atherosclerotic plaques from Rac2 -/-ApoE -/- mice contain increased inflammatory cellular infiltration by histology and relative RNA expression. Ex vivo microCT imaging reveals calcified aortic plaques, and quantification of calcification by near-infrared imaging demonstrates increased calcium composition in plaques from Rac2 -/-ApoE -/- mice relative to Rac2 +/+ApoE -/- mice. Calcified aortic plaques are associated with an increase in IL-1β mRNA expression in the aortic tissue. In summary, Rac2 is a critical modulator of signaling mechanisms that regulate the activation state of Rac1, resulting in enhanced macrophage IL-1β expression in vitro and inflammatory calcification of atherosclerotic plaques in vivo. Targeting the balance of Rac regulation has therapeutic potential in modulation of atherosclerotic plaque composition.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

1975 ◽  
Vol 33 ◽  
pp. 460-461
Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks
Keyword(s):  
Lipid Metabolism ◽  
New Zealand ◽  
Aortic Wall ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Metabolic Changes ◽  
Atherosclerotic Plaques ◽  
Cytochemical Study ◽  
Cellular Alteration ◽  
New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

Sign in / Sign up

Export Citation Format

Share Document