scholarly journals Anti-Galectin-2 antibody treatment reduces atherosclerotic plaque size and alters macrophage polarity

2021 ◽  
Author(s):  
Jamie Kane ◽  
Matthijs Jansen ◽  
Sebastian Hendrix ◽  
Laura A Bosmans ◽  
Linda Beckers ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Atherosclerotic Plaque ◽  
Therapeutic Interventions ◽  
Prolonged Treatment ◽  
High Cholesterol Diet ◽  
Plaque Size ◽  
Antibody Treatment ◽  
Fibrous Cap ◽  
Inflammatory Status ◽  
Anti Inflammatory

Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 blockade in ischaemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Galectin-2 may also affect other macrophage related cardiovascular diseases. This study aims to elucidate the effects of Galectin-2 inhibition in atherosclerosis. ApoE -/- mice were given a high cholesterol diet (HCD) for 12 weeks. After six weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama derived anti-Gal2 nanobodies (clones- 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Galectin-2 inhibition reduced the progression of existing atherosclerosis. Atherosclerotic plaque area in the aortic root was decreased, especially so in mice treated with 2C10 nanobodies. This clone reduced atherosclerosis severity as reflected by a decrease in fibrous cap atheromas in addition to decreases in plaque size. The number of plaque resident macrophages was unchanged, however, there was a significant increase in the fraction of CD206+ macrophages. 2C10 treatment also increased plaque α-smooth muscle content, and Gal-2 may have a role in modulating the inflammatory status of smooth muscle cells. Remarkably, both treatments reduced serum cholesterol concentrations including reductions in VLDL, LDL, and HDL whilst triglyceride concentrations were unchanged. Prolonged treatment with anti-Gal-2 nanobodies reduced plaque size, slowed plaque progression, and modified the phenotype of plaque macrophages toward an anti-inflammatory profile. These results hold promise for future macrophage modulating therapeutic interventions that promote arteriogenesis and reduce atherosclerosis.

Abstract 102: Cd98 Modulates Atherosclerotic Plaque Morphology by Regulating Smooth Muscle Cell Proliferation via the P-38 Map Kinase Pathway

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Sara McCurdy ◽  
Yvonne Baumer ◽  
Franz Hess ◽  
William A Boisvert
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Atherosclerotic Plaque ◽  
Necrotic Core ◽  
Plaque Morphology ◽  
Fibrous Cap ◽  
Plaque Area

Smooth muscle cells (SMC) are known to migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. It has been shown that CD98hc, a transmembrane protein with a known role in amino acid transport and integrin signaling, is involved in proliferation and survival of various cell types including SMC. Based on these data, we hypothesized that CD98hc deficiency selectively in SMC would have pathogenic effects on atherosclerosis development and plaque composition. To test this, we utilized mice with SMC-specific deletion of the CD98hc ( CD98hc fl/fl SM22Cre + ) to determine the effects of CD98hc deficiency on SMC function in the context of atherosclerosis. We performed in vitro proliferation and survival/apoptosis assays to investigate the role of CD98hc in the proliferation and survival of primary mouse aortic vascular smooth muscle cells. We found that VSMC isolated from whole aortas of CD98hc -/- animals displayed approximately 60% reduced cell counts compared to control (41 ± 8.2% of control) after 5 days in culture. EdU assays in vivo showed a defect in the ability of CD98hc -/- SMC to proliferate, with 25% reduction in EdU-positive VSMC compared to controls (2.3 ± 0.2% vs 3 ± 0.2%). In addition, caspase-3 staining of SMC in vitro displayed a 41% increase in propensity of CD98hc -/- SMC to undergo apoptosis compared to controls (7.9 ± 0.6% vs 5.6 ± 0.5%). Furthermore, the absence of CD98hc in SMC caused a sharp increase in phosphorylated p-38, which was partially abrogated towards control levels when the cells were treated with PDGF-BB to induce proliferation. Long-term atherosclerosis study using SMC-CD98hc -/- /LDLR -/- mice showed that atherosclerotic plaque morphology was altered with increased necrotic core area (25.8 ± 1.9% vs 10.9 ± 1.6% necrotic core area per plaque area) due to a reduction in infiltration of SMC within the plaque (2.1 ± 0.4% vs 4.3 ± 0.4% SM22α positive area per plaque area) compared to control LDLR -/- mice. These data support an important role for CD98hc and its regulation of p-38 MAP kinase signaling in aortic vascular smooth muscle cell proliferation and survival. We conclude that CD98hc is critical for the formation of fibrous cap that is important in maintaining the stability of atherosclerotic plaque.

Abstract 381: IL-19 Inhibits Atherosclerosis in LDLR-/- Mice by Modulating Cholesterol Uptake in Macrophages and Vascular Smooth Muscle Cells

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Khatuna Gabunia ◽  
Stephen P Ellison ◽  
James M Richards ◽  
Sheri E Kelemen ◽  
Michael V Autieri
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Plaque ◽  
Scavenger Receptor ◽  
Muscle Cells ◽  
Wild Type ◽  
Anti Inflammatory ◽  
M2 Phenotype

IL-19 is a recently described, putative anti-inflammatory cytokine which had previously been ascribed to be leukocyte specific. IL-19 is not detected in normal artery, but we detected IL-19 in multiple cell types in human atherosclerotic plaque suggesting a role for this interleukin in atherosclerosis. The purpose of this study was to determine whether administration of exogenous IL-19 could attenuate development of pre-formed atherosclerotic plaque, and to identify potential molecular mechanisms. LDLR-/- mice were fed high-fat diet for 12 weeks and then administered with 10ng/g/day IL-19 or PBS for an additional 8 weeks. En face analysis demonstrated that IL-19 could halt, but not reverse existing plaque (26.7+/-1.7%, 41.03+/-3.1%, 23.70+/-2.6% for baseline, PBS control, and IL-19-treated mice). Foam cell formation by macrophages and vascular smooth muscle cells (VSMC) is a hallmark event during atherosclerosis. Nothing has been reported regarding IL-19 effects on macrophage or VSMC lipid uptake; we therefore investigated whether IL-19 affects macrophage and VSMC cholesterol handling. Addition of IL-19 to wild-type bone marrow derived macrophages (BMDM) significantly promoted oxLDL uptake, conversely, BMDM from IL-19-/- mice had significantly less oxLDL uptake compared to wild-type BMDM. Addition of IL-19 to wild type BMDM significantly increased expression of scavenger receptor B1 (SR-B1), and decreased expression of inflammatory cytokines TNFα, IL-12b, MCP1. Interestingly, converse results were obtained with VSMC, as addition of IL-19 to wild-type VSMC decreased uptake of oxLDL ( p<0.05 ) and decreased expression of scavenger receptor CD36. VSMC isolated from IL-19-/- mice had increased uptake of oxLDL (p<0.0001). It is reported that M2 macrophages participate in plaque regression. IL-19 decreased IL-12b and significantly promoted the polarization of anti-inflammatory M2 phenotype in BMDM as evidenced by the increased expression of YM1 and IL-10 mRNA. These data demonstrate that IL-19 can inhibit progression of existing atherosclerotic plaque by modulating lipid metabolism in VSMC and macrophages and by promoting macrophage differentiation into an alternative, anti-inflammatory M2 phenotype.

scholarly journals Follicular regulatory helper T cells control the response of regulatory B cells to a high-cholesterol diet

2020 ◽  
Author(s):  
Fabienne Burger ◽  
Kapka Miteva ◽  
Daniela Baptista ◽  
Aline Roth ◽  
Rodrigo A Fraga-Silva ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Atherosclerotic Plaque ◽  
Helper T Cells ◽  
Cell Populations ◽  
High Cholesterol Diet ◽  
Plaque Size ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Cell Functions

Abstract Aims B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified. Methods and results In this study, we show that follicular regulatory helper T cells (TFR) control regulatory B cell (BREG) populations in Apoe−/− mice models on a high-cholesterol diet (HCD). Feeding mice with HCD resulted in up-regulation of TFR and BREG cell populations, causing the suppression of proatherogenic follicular helper T cell (TFH) response. TFH cell modulation is correlated with the growth of atherosclerotic plaque size in thoracoabdominal aortas and aortic root plaques, suggesting that TFR cells are atheroprotective. During adoptive transfer experiments, TFR cells transferred into HCD mice decreased TFH cell populations, atherosclerotic plaque size, while BREG cell population and lymphangiogenesis are significantly increased. Conclusion Our results demonstrate that, through different strategies, both TFR and TFH cells modulate anti- and pro-atherosclerotic immune processes in an Apoe−/− mice model since TFR cells are able to regulate both TFH and BREG cell populations as well as lymphangiogenesis and lipoprotein metabolism.

Processing of Chimeric Antisense Oligonucleotides by Human Vascular Smooth Muscle Cells and Human Atherosclerotic Plaque

Circulation ◽  
1996 ◽  
Vol 93 (4) ◽  
pp. 772-780 ◽  
Author(s):  
J. Geoffrey Pickering ◽  
Jeffrey M. Isner ◽  
Carol M. Ford ◽  
Lawrence Weir ◽  
Andrew Lazarovits ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Plaque ◽  
Antisense Oligonucleotides ◽  
Muscle Cells ◽  
Human Atherosclerotic Plaque

scholarly journals Ethosomes and Transethosomes for Mangiferin Transdermal Delivery

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 768
Author(s):  
Maddalena Sguizzato ◽  
Francesca Ferrara ◽  
Supandeep Singh Hallan ◽  
Anna Baldisserotto ◽  
Markus Drechsler ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Radical Scavenging ◽  
Human Keratinocytes ◽  
Antioxidant Response ◽  
Correlation Spectroscopy ◽  
Inflammatory Status ◽  
Transmission Electron ◽  
Anti Inflammatory

Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.

scholarly journals Curcumin and Freshwater Clam Extracts Alleviate the Progression of Osteoarthritis by Reducing Synovial Inflammation and Allowing Cartilage Regeneration

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 931
Author(s):  
Chiao-Hsu Ke ◽  
Chia-Hui Hsu ◽  
Yu-Ling Lin ◽  
Wei-Hsiang Huang ◽  
Hsin-Pei Weng ◽  
...  
Keyword(s):  
Scoring System ◽  
Inflammatory Diseases ◽  
Synergistic Effects ◽  
Symptomatic Relief ◽  
Cartilage Regeneration ◽  
Research Society ◽  
Infrapatellar Fat Pad ◽  
Freshwater Clam ◽  
Inflammatory Status ◽  
Anti Inflammatory

Osteoarthritis (OA) is a common degenerative disorder and is accompanied by numerous pain symptoms. With increased age, individuals develop a chronic inflammatory status, and pro-inflammatory cytokines as well as mediators contribute to the progression of OA. However, no desirable remedies have been completely able to inhibit OA progression or safely provide effective symptomatic relief. Natural component extracts or dietary-derived compounds are widely used for anti-inflammatory diseases. Curcumin and freshwater clam extract (FCE) have been proven as functional foods that are able to regulate immune systems. This study demonstrated that curcumin and FCE had synergistic effects on alleviating the progression of OA by assuaging inflammation and repairing the cartilage within the joints. After consumption of curcumin and FCE, the severity of synovitis was quantified by the infrapatellar fat pad inflammation scoring system and the Osteoarthritis Research Society International (OARSI) scoring system. Significant improvement and articular cartilage regeneration were noted. Moreover, once the inflammation within the joints was reduced, the animals redistributed their body weight on the OA-induced hindlimb. In summary, curcumin and FCE possess desirable anti-inflammatory and repair functions, suggesting their potential as alternative remedies in the management of OA or other inflammatory diseases.

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