NADPH oxidase is upregulated in smooth muscle cells (SMCs) in response to growth factor stimulation, concomitant with increased reactive oxygen species (ROS) production. We investigated the role of ROS production by NADPH oxidase in SMC responses to growth factors and in atherosclerotic lesion formation in ApoE–/– mice. SMCs from wild-type, p47phox–/–, and gp91phox–/– mice differed markedly with respect to growth factor responsiveness and ROS generation. p47phox–/– SMCs had diminished superoxide production and a decreased proliferative response to growth factors compared with wild-type cells, whereas the response of gp91phox–/– SMCs was indistinguishable from that of wild-type SMCs. The relevance of these in vitro observations was tested by measuring atherosclerotic lesion formation in genetically modified (wild-type, p47phox–/–, ApoE–/–, and ApoE–/–/p47phox–/–) mice. ApoE–/–/p47phox–/– mice had less total lesion area than ApoE–/– mice, regardless of whether mice were fed standard chow or a high-fat diet. Together, these studies provide convincing support for the hypothesis that superoxide generation in general, and NADPH oxidase in particular, have a requisite role in atherosclerotic lesion formation, and they provide a rationale for further studies to dissect the contributions of ROS to vascular lesion formation.
Patricia A. Barry-Lane, Cam Patterson, Marié van der Merwe, Zhaoyong Hu, Stephen M. Holland, Edward T.H. Yeh, Marschall S. Runge
Usage data is cumulative from April 2023 through April 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 411 | 60 |
73 | 32 | |
Figure | 143 | 14 |
Table | 18 | 0 |
Supplemental data | 36 | 2 |
Citation downloads | 19 | 0 |
Totals | 700 | 108 |
Total Views | 808 |
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.