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Examination by the Magnus test demonstrated dysfunction of endothelial cells (ECs) in the IL-18KO thoracic aorta and impairment of the anticontractile function of IL-18KO PVAT. Histological examination showed no inflammatory lesions in the aorta but indicated progressive fibrosis in the vessel and conversion of PVAT from brown adipose tissue-like features to white adipose tissue-like features. Electron microscopic observation suggested several deformed mitochondria in the aorta and vacuole-like structures in ECs from IL-18KO mice. In addition, activity of complex IV was lower and production of reactive oxygen species was augmented in the mitochondria of IL-18KO aorta. Although expression of LC3 B was higher, rapamycin-induced autophagy flux was impaired in the IL-18KO PVAT. Moreover, Western blot analysis revealed that LAMP 1\/2 was increased in IL-18KO PVAT, and measurement of cathepsin-D activity indicated decreased levels in IL-18KO PVAT. The IL-18KO thoracic aorta thus showed defects in physiological functions related to histological alterations, and the inflammasome\/IL-18 system was suggested to play a protective role in cardiovascular cells, probably through quality control of mitochondria via promotion of autophagosome\/autophagolysosome formation.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY IL-18 deficiency caused aortic abnormalities in terms of morphology and functions in parallel with an accumulation of damaged mitochondria and anomalous turnover of protein complexes, such as PGC-1 and LAMP1 and -2 in PVAT. These findings suggested that IL-18 plays roles in maintaining the homeostasis of vessels and PVAT around the aorta, possibly by promoting autophagy.<\/jats:p>","DOI":"10.1152\/ajpheart.00813.2018","type":"journal-article","created":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T17:56:46Z","timestamp":1568397406000},"page":"H1142-H1156","source":"Crossref","is-referenced-by-count":12,"title":["Impaired function of aorta and perivascular adipose tissue in IL-18-deficient mice"],"prefix":"10.1152","volume":"317","author":[{"given":"Wen","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan"},{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, Takatsuki, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, 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