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A genetic\n                    <jats:italic>LAMP2<\/jats:italic>\n                    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\u2013deficient mice and cultured cells. LAMP-2\u2013deficient mice at 9\u201324 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 (\n                    <jats:italic>i<\/jats:italic>\n                    .\n                    <jats:italic>e<\/jats:italic>\n                    ., mitochondria). The VSMC in\n                    <jats:italic>Lamp2<\/jats:italic>\n                    null mice expressed more vimentin but less \u03b1-smooth muscle actin (\u03b1-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of\n                    <jats:italic>LAMP2<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-21602-8","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T05:26:00Z","timestamp":1518585960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency"],"prefix":"10.1038","volume":"8","author":[{"given":"Huan T.","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Sugie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyen T. 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