Postnatal inflammation following intrauterine inflammation exacerbates the development of atherosclerosis in ApoE−/− mice

2019 ◽  
Vol 133 (10) ◽  
pp. 1185-1196 ◽  
Author(s):  
Siroon Bekkering ◽  
Albert P. Limawan ◽  
Maria U. Nguyen ◽  
Lisa K. Widiasmoko ◽  
Hui Lu ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Early Life ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Chronic Inflammatory Disease ◽  
Mechanistic Studies ◽  
Human Infants ◽  
Size Number ◽  
Severe Atherosclerosis ◽  
Apoe Knockout Mice

Abstract Atherosclerosis is a chronic inflammatory disease that has its origins in early life. Postnatal inflammation exacerbates atherosclerosis, but the possible effect of intrauterine inflammation is largely unexplored. Exposure to inflammation in utero is common, especially in infants born preterm, who have increased cardiovascular risk in adulthood. We hypothesised that exposure to inflammation before birth would accelerate the development of atherosclerosis, with the most severe atherosclerosis following exposure to both pre- and postnatal inflammation. Here we studied the effect of prenatal and postnatal inflammation on the development of atherosclerosis by combining established techniques for modelling histological chorioamnionitis and atherosclerosis using apolipoprotein E (ApoE) knockout mice. A single intra-amniotic (IA) injection of lipopolysaccharide (LPS) caused intrauterine inflammation, and increased atherosclerosis at 13 weeks of postnatal age. In mice exposed to postnatal LPS, chorioamnionitis modulated subsequent responses; atherosclerotic lesion size, number and severity were greatest for mice exposed to both intrauterine and postnatal inflammation, with a concomitant decrease in collagen content and increased inflammation of the atherosclerotic plaque. In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies.

PO9-223 TNF-LIKE INDUCER OF APOPTOSIS (TWEAK) INCREASES ATHEROSCLEROTIC LESION SIZE AND INFLAMMATION IN APOE KNOCKOUT MICE

2007 ◽  
Vol 8 (1) ◽  
pp. 72
Author(s):  
B. Muñoz-García ◽  
O. Lopez-Franco ◽  
J.L. Martín-Ventura ◽  
J.A. Moreno ◽  
J. Egido ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Apoe Knockout Mice

1.P.79 The effect of lacidipine on atherosclerotic lesion progression in apoE knockout mice

1997 ◽  
Vol 134 (1-2) ◽  
pp. 33 ◽  
Author(s):  
P. Cristofori ◽  
A. Lanzoni ◽  
D. Spagnolo ◽  
L. Cominacini ◽  
A. Pastorino ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Apoe Knockout Mice

HDL is essential for atherosclerotic lesion regression in Apoe knockout mice by bone marrow Apoe reconstitution

2018 ◽  
Vol 278 ◽  
pp. 240-249 ◽  
Author(s):  
Ronald J. van der Sluis ◽  
Robin A.F. Verwilligen ◽  
Zsuzsanna Lendvai ◽  
Robbert Wever ◽  
Menno Hoekstra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Apoe Knockout Mice ◽  
Lesion Regression

scholarly journals Low-Cholesterol and High-Fat Diets Reduce Atherosclerotic Lesion Development in ApoE-Knockout Mice

1999 ◽  
Vol 19 (10) ◽  
pp. 2368-2375 ◽  
Author(s):  
Lucía Calleja ◽  
Miguel A. París ◽  
Antoni Paul ◽  
Elisabet Vilella ◽  
Jorge Joven ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
High Fat ◽  
Lesion Development ◽  
High Fat Diets ◽  
Apoe Knockout Mice ◽  
Fat Diets ◽  
Low Cholesterol ◽  
Atherosclerotic Lesion Development

scholarly journals Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

2018 ◽  
Vol 59 (4) ◽  
pp. 658-669 ◽  
Author(s):  
Fu-Han Gong ◽  
Wen-Lin Cheng ◽  
Haiping Wang ◽  
Maomao Gao ◽  
Juan-Juan Qin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Knockout Mice ◽  
Noncoding Rna ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Endothelial Cell Proliferation ◽  
Double Knockout

Atherosclerosis is considered to be a chronic inflammatory disease that can lead to severe clinically important cardiovascular events. miR-150 is a small noncoding RNA that significantly enhances inflammatory responses by upregulating endothelial cell proliferation and migration, as well as intravascular environmental homeostasis. However, the exact role of miR-150 in atherosclerosis remains unknown. Here, we investigated the effect of miR-150 deficiency on atherosclerosis development. Using double-knockout (miR-150−/− and ApoE−/−) mice, we measured atherosclerotic lesion size and stability. Meanwhile, we conducted in vivo bone marrow transplantation to identify cellular-level components of the inflammatory response. Compared with mice deficient only in ApoE, the double-knockout mice had significantly smaller atherosclerotic lesions and displayed an attenuated inflammatory response. Moreover, miR-150 ablation promoted plaque stabilization via increases in smooth muscle cell and collagen content and decreased macrophage infiltration and lipid accumulation. The in vitro experiments indicated that an inflammatory response with miR-150 deficiency in atherosclerosis results directly from upregulated expression of the cytoskeletal protein, PDZ and LIM domain 1 (PDLIM1), in macrophages. More importantly, the decreases in phosphorylated p65 expression and inflammatory cytokine secretion induced by miR-150 ablation were reversed by PDLIM1 knockdown. These findings suggest that miR-150 is a promising target for the management of atherosclerosis.

MS152 DEFICIENCY OF NPP1 ATTENUATES ATHEROSCLEROTIC LESION PROGRESSION IN apoE KNOCKOUT MICE

2010 ◽  
Vol 11 (2) ◽  
pp. 140
Author(s):  
Y. Nitschke ◽  
G. Weissen-Plenz ◽  
R. Terkeltaub ◽  
F. Rutsch
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Apoe Knockout Mice

scholarly journals Overexpression of NF-κB p65 in macrophages ameliorates atherosclerosis in apoE-knockout mice

2013 ◽  
Vol 305 (11) ◽  
pp. E1375-E1383 ◽  
Author(s):  
Xin Ye ◽  
Xiaoting Jiang ◽  
Wei Guo ◽  
Katie Clark ◽  
Zhanguo Gao
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Knockout Mice ◽  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Apoe Knockout Mice

The transcription factor NF-κB p65 is a key regulator in the regulation of an inflammatory response and in the pathology of atherosclerosis. However, there is no direct evidence for the role of NF-κB in macrophages in the development of atherosclerosis. We investigated whether macrophage overexpression of p65 in apoE-knockout mice could improve atherosclerosis. Transgenic (Tg) mice overexpressing p65 in macrophages were generated by crossing fatty acid-binding protein 4 (aP2) promoter-controlled p65 mice with apoE-knockout (KO) mice. Tg mice exhibited functional activation of NF-κB signaling in macrophages and fat tissues. We observed that the atherosclerotic lesion was 40% less in the Tg mice compared with the apoE-KO controls fed a standard atherogenic diet for 16 wk ( n = 12). The Tg mice were leaner from reduced fat mass by increased energy expenditure. Moreover, the overexpression of p65 in macrophages suppressed foam cell formation. Our results show that there is 1) an increased fatty acid oxidation in macrophages, 2) a reduced scavenger receptor CD36 expression and lipid accumulation in microphages, 3) reduced-inflammation cytokines in serum, and 4) enhanced energy expenditure in Tg mice. Our data suggest that activation of NF-κB in macrophages has atheroprotective effects in mice by enhancing lipid metabolism and energy expenditure.

scholarly journals Dulaglutide exerts beneficial anti atherosclerotic effects in ApoE knockout mice with diabetes: the earlier, the better

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junpei Sanada ◽  
Atsushi Obata ◽  
Yoshiyuki Obata ◽  
Yoshiro Fushimi ◽  
Masashi Shimoda ◽  
...  
Keyword(s):  
Early Intervention ◽  
Knockout Mice ◽  
Aortic Root ◽  
Late Phase ◽  
Intervention Group ◽  
Atherosclerotic Lesion ◽  
Expression Levels ◽  
Late Intervention ◽  
Apoe Knockout Mice ◽  
Early Intervention Group

AbstractThere has been no report about the mechanism for anti-atherosclerotic effects of dulaglutide (Dula) and/or about the difference of its effectiveness between in an early and a late phase of diabetes. To address such questions, streptozotocin (STZ) was intraperitoneally injected to ApoE knockout mice at 8 weeks of age. Either Dula or vehicle was administered to STZ-induced diabetic ApoE knockout mice from 10 to 18 weeks of age as an early intervention group and from 18 to 26 weeks as a late intervention group. Next, non-diabetic ApoE knockout mice without STZ injection were subcutaneously injected with either Dula or vehicle. In an early intervention group, atherosclerotic lesion in aortic arch and Mac-2 and CD68-positive areas in aortic root were significantly smaller in Dula group. In abdominal aorta, expression levels of some villain factors were lower in Dula group. In a late intervention group, there were no immunohistological differences in aortic root and expression levels of various factors between two groups. Furthermore, even in non-diabetic ApoE knockout mice, expression levels of inflammatory and macrophage markers were reduced by treatment with Dula. Taken together, Dula exerts more beneficial anti-atherosclerotic effects in an early phase of diabetes rather than in a late phase.

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