RIMKLA promotes hypertension by activating PKM2 to trigger VSMC phenotype switch

Area of Science:

• Cardiovascular Biology
• Molecular Mechanisms of Disease
• Metabolic Regulation

Background:

• Hypertension affects over a billion adults globally.
• Abnormal glucose metabolism and vascular smooth muscle cell (VSMC) phenotype switching are key to hypertension.
• The role of pyruvate kinase M2 (PKM2) in VSMC phenotype switch and hypertension remains unclear.

Purpose of the Study:

• To investigate the role of ribosomal modification protein rimK-like family member A (RIMKLA) in hypertension.
• To elucidate the regulatory mechanisms of RIMKLA in VSMC phenotype switching and arterial function.

Main Methods:

• Analysis of arterial tissues from hypertensive patients and animal models.
• Gene manipulation (overexpression and knockout) in VSMCs and in vivo.
• Assessment of blood pressure, arterial contractility, and molecular signaling pathways.
• Identification of protein-protein interactions and metabolic changes.

Main Results:

• RIMKLA expression is elevated in hypertensive arteries.
• RIMKLA overexpression increases arterial contractility and blood pressure.
• RIMKLA acts as a scaffold, recruiting PTP1B and PKM2 to activate PKM2.
• Activated PKM2 enhances glucose metabolism, increases ROS, and drives VSMC phenotype switch, leading to hypertension.

Conclusions:

• RIMKLA is a critical regulator of PKM2 activation via a scaffold mechanism.
• RIMKLA promotes VSMC phenotype switching and contributes significantly to hypertension.
• Targeting the RIMKLA-PKM2 axis may offer therapeutic strategies for hypertension.