Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses

Izawa‐Ishizawa, Yuki; Imanishi, Masaki; Zamami, Yoshito; Toya, Hiroki; Nagao, Taeko; Morishita, Marin; Tsuneyama, Koichi; Horinouchi, Yuya; Kihira, Yoshitaka; Takechi, Kenshi; Ikeda, Yasumasa; Tsuchiya, Koichiro; Yoshizumi, Masanori; Takahashi, Toshiaki; Ishizawa, Keisuke

doi:10.1097/hjh.0000000000001898

Cited by 31 publications

(29 citation statements)

References 28 publications

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“…In a previous study, we reported that an increase in nitric oxide may upregulate the expression of the cell junction molecule, vascular endothelial cadherin, via ERK5 expression and protect the endothelium from vascular hyperpermeability [ 6 ]. Pitavastatin phosphorylates ERK5 directly and activates its downstream pathways including eNOS expression [ 6 ]. In the present study, we have showed that quercetin activated ERK5 to the same extent as pitavastatin ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…The mRNA expression levels in the aortas or culture cells were analyzed by real-time PCR, as described previously [ 6 ]. Sequences of the amplification primer pairs are as shown in Table 3 .…”

Section: Methodsmentioning

confidence: 99%

“…Aortic dissection is a condition in which the aortic wall is separated into two layers at the level of the media, resulting in the formation of a true lumen and false lumen [ 4 ]. Although the cause of dissection is considered to be similar to that of aneurysms, endothelial dysfunction also plays an important role in the onset of dissection [ 6 , 7 ]. In our previous study, we established a novel aortic dissection-prone model mouse that is pharmacologically induced by loading angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to cause hypertension and degeneration of the elastic lamina, respectively, resulting in the onset of an aortic aneurysm [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, we established a novel aortic dissection-prone model mouse that is pharmacologically induced by loading angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to cause hypertension and degeneration of the elastic lamina, respectively, resulting in the onset of an aortic aneurysm [ 8 ]. The addition of N ω-nitro- l -arginine methyl ester ( l -NAME), a nitric oxide synthase (NOS) inhibitor, to this aneurysm model increases the incidence of aortic dissection and aortic rupture due to endothelial dysfunction [ 6 ]. We have previously reported that the lipid-lowering drug pitavastatin can inhibit the onset of aortic dissection through its endothelium-protecting and anti-inflammatory effects [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The addition of N ω-nitro- l -arginine methyl ester ( l -NAME), a nitric oxide synthase (NOS) inhibitor, to this aneurysm model increases the incidence of aortic dissection and aortic rupture due to endothelial dysfunction [ 6 ]. We have previously reported that the lipid-lowering drug pitavastatin can inhibit the onset of aortic dissection through its endothelium-protecting and anti-inflammatory effects [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

Kondo

Izawa‐Ishizawa

Goda

et al. 2020

IJMS

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Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

Kondo

Izawa‐Ishizawa

Goda

et al. 2020

IJMS

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Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

et al. 2020

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Background In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab‐treated patients and examined the impact on the therapeutic effect. Patients and methods We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells. Results There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect. Conclusion PPIs prevent hypertension in bevacizumab‐treated patients but may reduce bevacizumab's anti‐tumoral effects by inducing VEGF expression.

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The Satisfaction Evaluation Model of Course Resources of Automobile Maintenance Major Based on Big Data

Yong-ji

2020

Lecture Notes of the Institute for Computer Sciences, Social Informatics and Telecommunications Engineering

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Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses

Cited by 31 publications

References 28 publications

Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

The Satisfaction Evaluation Model of Course Resources of Automobile Maintenance Major Based on Big Data

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