ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Hypertension Research

Background:

• Hypertension is a major cardiovascular disease risk factor with unclear mechanisms.
• Zinc finger protein 36 (ZFP36) is an RNA-binding protein affecting mRNA stability.
• ZFP36 expression is elevated in arteries of hypertensive patients and rodents.

Purpose of the Study:

• To investigate the role of ZFP36 in hypertension.
• To elucidate the molecular mechanisms by which ZFP36 influences blood pressure regulation.

Main Methods:

• Studied ZFP36 expression in hypertensive patients and rodents.
• Utilized cultured vascular smooth muscle cells (VSMCs) and angiotensin II (AngII) stimulation.
• Employed VSMC-specific ZFP36 deletion and AAV-mediated ZFP36 knockdown in mouse and rat models.
• Assessed vascular contractility, blood pressure, intracellular calcium levels, and RGS2 mRNA stability.

Main Results:

• ZFP36 expression is significantly elevated in hypertensive arteries.
• Angiotensin II stimulates ZFP36 expression in VSMCs via PARP1 activation.
• VSMC-specific ZFP36 deletion reduced blood pressure and vascular contractility in mice.
• ZFP36 impairs RGS2 mRNA stability, affecting calcium signaling.
• ZFP36 deficiency attenuated AngII-induced hypertension and vascular remodeling.
• ZFP36 knockdown ameliorated spontaneous hypertension in rats.

Conclusions:

• ZFP36 plays a critical role in regulating vascular smooth muscle contraction and blood pressure.
• ZFP36 modulates blood pressure by affecting RGS2 expression and calcium signaling.
• ZFP36 inhibition presents a promising therapeutic strategy for hypertension treatment.