| First Author | Li W | Year | 2019 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 317 |
| Issue | 5 | Pages | H1142-H1156 |
| PubMed ID | 31518161 | Mgi Jnum | J:310500 |
| Mgi Id | MGI:6762362 | Doi | 10.1152/ajpheart.00813.2018 |
| Citation | Li W, et al. (2019) Impaired function of aorta and perivascular adipose tissue in IL-18-deficient mice. Am J Physiol Heart Circ Physiol 317(5):H1142-H1156 |
| abstractText | IL-18 is ubiquitously produced by both hematopoietic and non-hematopoietic cells. The present study examined the thoracic aorta, including the surrounding perivascular adipose tissue (PVAT), of IL-18KO mice from functional and histological perspectives. IL-18KO mice exhibited raised blood pressure compared with wild-type mice. Echocardiographic examination showed a thickened vascular wall and narrowed vascular diameter of the aorta. 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.NEW & 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. |
