YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy.

Area of Science:

• Cardiovascular Biology
• Vascular Mechanobiology
• Molecular Mechanisms of Hypertension

Background:

• Hypertension is a major cardiovascular disease risk factor with poorly understood mechanisms.
• Vascular smooth muscle cell (VSMC) mechanotransduction and contractile function are vital for vascular integrity.
• The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) are mechanosensitive coactivators, but their in vivo role in VSMC mechanotransduction is unknown.

Purpose of the Study:

• To investigate the in vivo role of YAP/TAZ in VSMC mechanotransduction.
• To determine the contribution of YAP/TAZ to vascular integrity and response to hypertensive stimuli.

Main Methods:

• Generation of an inducible smooth muscle-specific YAP/TAZ knockout mouse model.
• Physiological and molecular analyses of vascular function and structure.
• Assessment of arterial contraction, myogenic response, and transcriptional regulation.

Main Results:

• Arteries lacking YAP/TAZ exhibited reduced contraction and impaired stretch-induced gene regulation.
• YAP/TAZ knockout in hypertension led to severe vascular lesions, including neointimal hyperplasia and elastin degradation.
• These findings indicate a critical role for YAP/TAZ in maintaining vascular wall integrity under hypertensive conditions.

Conclusions:

• YAP/TAZ play a crucial protective role against hypertensive vasculopathy.
• Proper VSMC mechanotransduction mediated by YAP/TAZ is essential for preventing vascular damage in hypertension.