| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2020-08-26 |
| タイトル |
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|
タイトル |
Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency |
| タイトル |
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タイトル |
Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_46ec |
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資源タイプ |
thesis |
| 別タイトル |
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その他のタイトル |
ライソゾーム関連蛋白 LAMP-2 欠損に基づくオートファジー異常 による小血管硬化の発症機序 |
| 著者 |
Nguyen, Than Huan
Nguyen, Huan T.
Noguchi, Satoru
Sugie, Kazuma
Matsuo, Yoshiyuki
Nguyen, Chuyen T. H.
Koito, Hitoshi
Shiojima, Ichiro
Nishino, Ichizo
Tsukaguchi, Hiroyasu
|
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2–deficient mice and cultured cells. LAMP-2–deficient mice at 9–24 months of age showed medial thickening with luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in Lamp2 null mice expressed more vimentin but less α-smooth muscle actin (α-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of LAMP2 in cultured human brain VSMC showed the same phenotypic transition with mitochondrial fragmentation, enhanced mitochondrial respiration, and overproduction of reactive oxygen species (ROS). These findings indicate that LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic conversion of VSMC, resulting from age-dependent accumulation of cellular waste generated by aberrant autophagy. |
| 学位名 |
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学位名 |
博士(医学) |
| 学位授与機関 |
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学位授与機関名 |
関西医科大学 |
| 学位授与年度 |
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内容記述タイプ |
Other |
|
内容記述 |
平成29年度 |
| 学位授与年月日 |
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学位授与年月日 |
2018-03-27 |
| 学位授与番号 |
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学位授与番号 |
課博第1021号 |
| 書誌情報 |
Scientific Reports
en : Scientific Reports
巻 8,
号 1,
発行日 2018
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| DOI |
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10.1038/s41598-018-21602-8 |
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https://doi.org/10.1038/s41598-018-21602-8 |
論文要旨（要約） (166.7 kB)
