scholarly journals Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2224
Author(s):  
Makoto Saburi ◽  
Hiroyuki Yamada ◽  
Naotoshi Wada ◽  
Shinichiro Motoyama ◽  
Takeshi Sugimoto ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
Specific Gene ◽  
Positive Staining ◽  
Adult Offspring ◽  
High Fat ◽  
Activated T Cells ◽  
Abdominal Aortic ◽  
The Impact

Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.

P732Maternal high-fat diet promotes the expansion of abdominal aortic aneurysm in adult offspring by enhancing osteoclast-like macrophage differentiation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Saburi ◽  
H Yamada ◽  
N Wada ◽  
S Motoyama ◽  
T Sugimoto ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
Fold Increase ◽  
Adult Offspring ◽  
High Fat ◽  
Double Positive ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Outer Circumference

Abstract Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating and received during pregnancy and lactation. In eight-week-old offspring of both genders, AAA was induced with the application of 0.5M calcium chloride (CaCl2) on the infrarenal aorta. Male offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND) (P<0.05). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (P<0.05). Likewise, female O-HFD showed a greater length of outer circumference than female O-ND (P<0.05). While the number of F4/80-positive cells at 1 wk after surgery was comparable between the male O-HFD and O-ND, the percentage of MMP-9/F4/80 double-positive cells was significantly increased in male O-HFD. Consistently, fluorescent image of abdominal aorta taken by IVIS at 1 wk after surgery revealed a 2-fold increase in MMP activity (P<0.01). Intriguingly, F4/80-positive cells in male O-HFD showed a 2.5-fold increase in co-staining with tartrate-resistant acid phosphate (TRAP), typical marker of osteoclast-like macrophages which abundantly secrete proteases than classically activated macrophages (M1), while the percentage of TNF-α/F4/80 double-positive cells was comparable between the 2 groups. Pharmacological inhibition of osteoclastogenesis by zoledronic acid (ZA) (100μg/kg) completely abolished the exaggerated AAA development in male O-HFD to a similar extent of that in male O-ND, while AAA development in male O-ND mice did not change even after ZA treatment. Furthermore, in vitro TNF-α-induced osteoclast differentiation of bone marrow-derived macrophages (BMDMs) showed a significantly higher number of TRAP-positive cells, accompanied by increased calcitonin receptor mRNA expression. Western blotting analysis showed that protein expression level of NFATc1, master regulator of osteoclastogenesis, was significantly higher in BMDM of O-HFD than O-ND. Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development.

Maternal high-fat diet promotes the expansion of abdominal aortic aneurysm in adult offspring by enhancing osteoclast-like macrophage differentiation through down-regulation of IRF8 expression

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Saburi ◽  
H Yamada ◽  
T Sugimoto ◽  
H Kubota ◽  
D Miyawaki ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
Fold Increase ◽  
Adult Offspring ◽  
High Fat ◽  
Double Positive ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Outer Circumference

Abstract Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and the diet was continued throughout gestation and lactation. In eight-week-old male offspring, AAA was induced with the application of 0.5 M calcium chloride (CaCl2) on the infrarenal aorta. Offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (p&lt;0.05). Likewise, female O-HFD showed a greater length of outer circumference than female O-ND (p&lt;0.05). While the number of F4/80-positive cells at 1 wk after surgery was comparable in the O-HFD and O-ND, the percentage of MMP-9/F4/80 double-positive cells was significantly increased in O-HFD. Consistently, fluorescent image of abdominal aorta taken by IVIS at 1 wk after surgery revealed a 2-fold increase in MMP activity. Intriguingly, F4/80-positive cells in O-HFD showed a 2.5-fold increase in co-staining with tartrate-resistant acid phosphate (TRAP), typical marker of osteoclast-like macrophages which abundantly secrete proteases than classically activated macrophages, while the percentage of TNF-α/F4/80 double-positive cells was comparable in the two groups. Pharmacological inhibition of osteoclastogenesis by zoledronic acid (ZA) (100μg/kg) completely abolished the exaggerated AAA development in O-HFD to an extent similar to that in O-ND, while AAA development in O-ND mice did not change after ZA treatment. Furthermore, in vitro TNF-α-induced osteoclast differentiation of bone marrow-derived macrophages (BMDMs) showed a significantly higher number of TRAP-positive cells in O-HFD, accompanied by a significant increase in osteoclast-related genes expression. Western blotting analysis revealed that the expression of NFATc1, master regulator of osteoclastogenesis, was significantly higher in O-HFD than that in O-ND, and immunofluorescent imaging showed that nuclear translocation of NFATc1 upon TNF-α stimulation was significantly enhanced in O-HFD. We further examined the expression of IFN regulatory factor 8 (IRF8) which suppresses osteoclastogenesis by inhibiting the function and expression of NFATc1. IRF8 mRNA and nuclear protein expression levels were significantly lower in O-HFD than those in O-ND. Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development. Funding Acknowledgement Type of funding source: None

The Effect of a High-Fat Diet on the Development of Abdominal Aortic Aneurysm in a Vascular Hypoperfusion-Induced Animal Model

2018 ◽  
Vol 55 (2) ◽  
pp. 63-74 ◽  
Author(s):  
Keisuke Hashimoto ◽  
Hirona Kugo ◽  
Hiroki Tanaka ◽  
Kazuko Iwamoto ◽  
Chie Miyamoto ◽  
...  
Keyword(s):  
Animal Model ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
High Fat ◽  
Abdominal Aortic ◽  
Vascular Hypoperfusion

Stereoscopically Observed Deformations of a Compliant Abdominal Aortic Aneurysm Model

2011 ◽  
Vol 133 (11) ◽  
Author(s):  
Clark A. Meyer ◽  
Eric Bertrand ◽  
Olivier Boiron ◽  
Valérie Deplano
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Computational Models ◽  
Imaging System ◽  
Strain Differences ◽  
Cyclic Strain ◽  
Experimental Models ◽  
Body Motion ◽  
Abdominal Aortic ◽  
The Impact

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07 mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120 mm Hg. These strains are 1–2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.

The impact of maternal high-fat feeding on liver and abdominal fat accumulation in adult offspring under a long-term high-fat diet

Hepatology ◽  
2009 ◽  
Vol 51 (6) ◽  
pp. 2234-2235 ◽  
Author(s):  
Adriana L. Burgueño ◽  
Julieta Carabelli ◽  
Silvia Sookoian ◽  
Carlos J. Pirola
Keyword(s):  
High Fat Diet ◽  
Abdominal Fat ◽  
Adult Offspring ◽  
High Fat ◽  
Fat Accumulation ◽  
The Impact ◽  
Fat Feeding

The Impact of an Abdominal Aortic Aneurysm on Aortic Wave Reflection

2007 ◽  
Author(s):  
Abigail Swillens ◽  
Lieve Lanoye ◽  
Julie De Backer ◽  
Nikos Stergiopulos ◽  
Frank Vermassen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wave Reflection ◽  
Numerical Models ◽  
Aortic Aneurysms ◽  
Western World ◽  
Parameter Study ◽  
Linear Wave ◽  
Abdominal Aortic ◽  
The Impact

The economical growth and increased welfare in the Western world have a reverse side, with an increased death toll due to cardiovascular diseases. Among these, aortic aneurysms (a local dilation) are particularly lethal as they may grow unnoticed until rupture occurs. In this study, we assessed the impact of the presence of an abdominal aortic aneurysm on arterial hemodynamics and wave reflection in particular. Experimental and numerical methods were applied. Linear wave separation was used to quantify the reflections; wave intensity analysis was applied to assess the nature of the reflected waves. In both the experimental and numerical models, negative reflections were found in the upper aorta corresponding to a backward expansion wave caused by the sudden expansion of the aorta. A numerical parameter study demonstrated that larger diameters and more compliant aneurysms generate stronger negative reflections.

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