CUL3 and hypertensive disorder: Remarkably, the restoration of RhoBTB1 on its own by a PPARγ-independent mechanism ameliorated adverse cardiovascular phenotypes in animals carrying a dominant-negative PPARγ mutation.15 RhoBTB1 is also downregulated in models of angiotensin-II mediated HTN and restoration of RhoBTB1 rapidly reverses arterial stiffness.16 This data clearly implicated vascular smooth muscle PPARγ-RhoBTB1-CUL3-PDE5 as an important regulator of arterial BP.