RhoBTB1 reverses established arterial stiffness in angiotensin II-induced hypertension by promoting actin...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Vascular Physiology

Background:

• Arterial stiffness is a predictor of cardiovascular disease and mortality.
• Angiotensin II (Ang II) treatment in mice induces hypertension, arterial stiffness, and vascular dysfunction, alongside reduced RhoBTB1.
• The precise role of RhoBTB1 in vascular health remains unclear.

Purpose of the Study:

• To investigate if restoring RhoBTB1 can mitigate arterial stiffness, hypertension, and vascular dysfunction in Ang II-treated mice.
• To elucidate the underlying mechanisms by which RhoBTB1 influences vascular properties.

Main Methods:

• Utilized a mouse model with tamoxifen-inducible, smooth muscle-specific RhoBTB1 transgene for genetic complementation.
• Administered Ang II to induce hypertension and arterial stiffness.
• Assessed arterial stiffness, blood pressure, vascular function, and aortic tissue for molecular changes.

Main Results:

• RhoBTB1 restoration effectively and quickly reduced arterial stiffness without significantly impacting hypertension or vascular dysfunction.
• RhoBTB1 did not alter major contributors to stiffness like collagen, elastin, or vascular smooth muscle remodeling.
• Ang II-induced actin polymerization in the aorta was reversed by RhoBTB1, suggesting an actin depolymerization mechanism.

Conclusions:

• RhoBTB1 plays a critical role in antagonizing established arterial stiffness.
• The findings support a functional and mechanistic distinction between hypertension, vascular dysfunction, and arterial stiffness.
• RhoBTB1's mechanism involves regulating actin polymerization, offering a novel therapeutic target for arterial stiffness.