Loss of Apoptosis Regulator through Modulating IAP Expression (ARIA) Protects Blood Vessels from Atherosclerosis

Matsuo, Kiyonari; Akakabe, Yoshiki; Kitamura, Yoshihisa; Shimoda, Yoshiaki; Ono, Kazunori; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Hatakeyama, Kinta; Asada, Yujiro; Emoto, Noriaki; Ikeda, Koji

doi:10.1074/jbc.m114.605287

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…Intima/media ratio was calculated by the linear measurements of intima and media thickness. Sequential sections were stained with Masson's trichrome for evaluation of collagen and the characteristics of atherogenesis including inflammatory cell infiltration, medial fibrosis and necrotic core as previously described 17-19 .…”

Section: Resultsmentioning

confidence: 99%

Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis

Hastürk

Abdallah

Kantarcı

et al. 2015

ATVB

182

161

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Objective Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared to diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by P. gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4μg/site or 0.4 μg/site) topically applied 3-times/ week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology and ex vivo MRI. Serum levels of C-reactive protein (CRP) were evaluated as a measure of systemic inflammation.RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (p<0.05). In the absence of periodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared to no-treatment (p<0.001). Local oral RvE1 application significantly reduced systemic levels of CRP (p<0.05). Conclusions The results suggest that oral/topical RvE1 attenuates enhanced atherogenesis induced by periodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events.

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Section: Resultsmentioning

confidence: 99%

Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis

Hastürk

Abdallah

Kantarcı

et al. 2015

ATVB

182

161

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“…Littermate ApoE-KO mice were always used as controls for ApoE-KO/TERF2DN-Tg mice. For en face analysis, the entire aorta from the heart, extending 5 mm after bifurcation of the iliac arteries and including the subclavian right and left common carotid arteries, was removed, dissected, and stained with oil red-O 38 . The oil red-O-positive atherosclerotic lesion area was measured using the Image J software.…”

Section: Methodsmentioning

confidence: 99%

Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis

Honda

Ikeda

Urata

et al. 2021

Sci Rep

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Senescent vascular cells are detected in atherosclerotic lesion, and its involvement in the development of atherosclerosis has been revealed; however, whether and the mechanism by which endothelial cell (EC) senescence is causally implicated in atherosclerosis remains unclear. We here investigate a role of EC senescence in atherosclerosis by utilizing EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 or vascular endothelial cadherin promoter. EC-specific progeria accelerated atherosclerosis in mice with target deletion of ApoE. Mechanistically, senescent ECs were markedly sensitive for inflammation-mediated VCAM-1 induction, leading to enhanced monocyte adhesion. Inhibition of NF-κB signaling abolished the enhanced inflammatory responses in senescent ECs, while NF-κB nuclear translocation in response to TNF-α were similar between young and senescent ECs. We found a higher association of VCAM-1 gene with active histone H3 trimethylated on lysine 4, leading to increased NF-κB accessibility in senescent ECs. Our data revealed that EC cellular senescence causes endothelial hyper-inflammability through epigenetic alteration, which consequently accelerates atherosclerosis. Therefore, EC senescence is a promising therapeutic target for the prevention and/or treatment of atherosclerotic disease in elderly population.

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“…ACAT-1 plays a key role in the formation of foam cells by catalyzing the esterification of free cholesterol to form cytoplasmic lipid droplets. Matsuo K et al identified a new protein and showed that ARIA ( Figure 2 ) deficiency attenuated the activity of PTEN, thereby enhancing the activation of PI3K/Akt, reducing the expression of ACAT-1 and reducing the formation of foam cells ( Matsuo et al, 2015 ). Wang J demonstrated that in vitro , miR-223 ( Figure 2 ) reversed macrophage-mediated lipid deposition and the inflammatory response by activating PI3K/AKT-mediated TLR4-NF-κB signaling ( Wang J. et al, 2015 ).…”

Section: Pi3k-targeted Therapy In Atherosclerosismentioning

confidence: 99%

Role of PI3K in the Progression and Regression of Atherosclerosis

et al. 2021

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Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

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Loss of Apoptosis Regulator through Modulating IAP Expression (ARIA) Protects Blood Vessels from Atherosclerosis

Cited by 6 publications

References 27 publications

Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis

Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis

Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis

Role of PI3K in the Progression and Regression of Atherosclerosis

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