Mice selectively expressing a PPARγ dominant-negative mutation in vascular smooth muscle exhibit RhoBTB1 deficiency and hypertension. Our rationale was to use genetic complementation to uncover the mechanism of action of RhoBTB1 in vascular smooth muscle. Inducible smooth muscle–specific restoration of RhoBTB1 fully corrected hypertension and arterial stiffness by improving vasodilator function. Notably, the cardiovascular protection occurred despite the preservation of increased agonist-mediated contraction and RhoA and Rho kinase activity, suggesting that RhoBTB1 selectively controls vasodilation. RhoBTB1 augmented the cyclic 3′,5′-monophosphate (cGMP) response to NO by restraining the activity of phosphodiesterase 5 (PDE5) through its action as a substrate adaptor delivering PDE5 to the Cullin-3 E3 ring ubiquitin ligase complex for ubiquitination, thereby inhibiting PDE5. Angiotensin II infusion also caused RhoBTB1 deficiency and hypertension, which were prevented by smooth muscle–specific RhoBTB1 restoration. We conclude that RhoBTB1 protected against hypertension, vascular smooth muscle dysfunction, and arterial stiffness in at least 2 models of hypertension.
Masashi Mukohda, Shi Fang, Jing Wu, Larry N. Agbor, Anand R. Nair, Stella-Rita C. Ibeawuchi, Chunyan Hu, Xuebo Liu, Ko-Ting Lu, Deng-Fu Guo, Deborah R. Davis, Henry L. Keen, Frederick W. Quelle, Curt D. Sigmund
Usage data is cumulative from March 2023 through March 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 722 | 147 |
164 | 37 | |
Figure | 227 | 4 |
Supplemental data | 22 | 8 |
Citation downloads | 30 | 0 |
Totals | 1,165 | 196 |
Total Views | 1,361 |
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.