Usage Information
Abstract
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine to xanthine and xanthine to uric acid, respectively. However, the underlying mechanisms of increased plasma XOR and its pathological roles in systemic diseases, such as atherosclerosis, are not fully understood. In this study, we found that changes in plasma XOR activity after bariatric surgery closely associated with those in liver enzymes, but not with those in BMI. In a mouse model of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), plasma XOR activity markedly increased. Besides, purine catabolism was accelerated in the plasma per se of NASH mice and human patients with high XOR activity. In our NASH mice, we observed an increased vascular neointima formation consisting of dedifferentiated vascular smooth muscle cells (SMCs), which was significantly attenuated by topiroxostat, a selective XOR inhibitor. In vitro, human liver S9–derived XOR promoted proliferation of SMCs with phenotypic modulation and induced ROS production by catabolizing hypoxanthine released from human endothelial cells. Collectively, the results from human and mouse models suggest that increased plasma XOR activity, mainly explained by excess hepatic leakage, was involved in the pathogenesis of vascular injury, especially in NAFLD/NASH conditions.
Authors
Yusuke Kawachi, Yuya Fujishima, Hitoshi Nishizawa, Takashi Nakamura, Seigo Akari, Takayo Murase, Takuro Saito, Yasuhiro Miyazaki, Hirofumi Nagao, Shiro Fukuda, Shunbun Kita, Naoto Katakami, Yuichiro Doki, Norikazu Maeda, Iichiro Shimomura
Usage data is cumulative from August 2025 through August 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,107 | 134 |
| 299 | 33 | |
| Figure | 1,347 | 0 |
| Supplemental data | 151 | 4 |
| Citation downloads | 295 | 0 |
| Totals | 4,199 | 171 |
| Total Views | 4,370 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
