2024-03-29T07:17:28Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00032075
2022-12-15T04:01:07Z
453:455
471:561:562
アムロジピンは血管細胞の老化を抑制し、カルシウムチャネルの遮断作用とは異なる機構を介してアテローム形成を予防する
Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade
Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade
Kayamori, Hiromi
175168
新潟大学
博士(医学)
Vascular cells have a finite lifespan and eventually enter irreversible growth arrest called cellular senescence. We have previously suggested that vascular cell senescence contributes to the pathogenesis of human atherosclerosis. Amlodipine is a mixture of two enantiomers, one of which (S- enantiomer) has L-type channel blocking activity, while the other (R+ enantiomer) shows ~1000-fold weaker channel blocking activity than Senantiomer and has other unknown effects. It has been reported that amlodipine inhibits the progression of atherosclerosis in humans, but the molecular mechanism of this beneficial effect remains unknown. Apolipoprotein E-deficient mice on a high-fat diet were treated with amlodipine, its R+ enantiomer or vehicle for eight weeks. Compared with vehicle treatment, both amlodipine and the R+ enantiomer significantly reduced the number of senescent vascular cells and inhibited plaque formation to a similar extent. Expression of the pro-inflammatory molecule interleukin-1βwas markedly upregulated in vehicle-treated mice, but was inhibited to a similar extent by treatment with amlodipine or the R+ enantiomer. Likewise, activation of p53 (a critical inducer of senescence) was markedly suppressed by treatment with amlodipine or the R+ enantiomer. These results suggest that amlodipine inhibits vascular cell senescence and protects against atherogenesis at least partly by a mechanism that is independent of calcium channel blockade.
学位の種類: 博士(医学). 報告番号: 甲第4540号. 学位記番号: 新大院博(医)甲第862号. 学位授与年月日: 平成31年3月25日
新大院博(医)甲第862号
thesis
新潟大学
2019-03-25
2019-03-25
application/pdf
application/pdf
13101甲第4540号
https://niigata-u.repo.nii.ac.jp/record/32075/files/h30nmk862.pdf
https://niigata-u.repo.nii.ac.jp/record/32075/files/h30nmk862_a.pdf
eng
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