What question did this study set out to answer?

The aim is to explore the role of SHP2 in AMPK dephosphorylation and its impact on ventricular remodeling.

January 10, 2026Cell Communication and Signaling0 citationsOpen Access

Inhibiting SHP2 improves ventricular remodeling by restoring AMPK phosphorylation and mitochondrial homeostasis

QSQiao-Juan ShiZhejiang Provincial People's Hospital WLWeiqi LiHangzhou Medical College YLYa-Nan LiuHangzhou Medical College

Key Result

Inhibition of SHP2 restored AMPK phosphorylation and improved mitochondrial function, which ameliorated ventricular remodeling in heart failure.

Key Points

The aim is to explore the role of SHP2 in AMPK dephosphorylation and its impact on ventricular remodeling.
Investigated the function of SHP2 as a phosphatase in cardiac tissue.
Assessed AMPK phosphorylation levels in response to SHP2 inhibition.
Analyzed the effects on mitochondrial function and ventricular structure.
Inhibition of SHP2 resulted in increased AMPK phosphorylation.
Improved mitochondrial function was observed.
Ventricular remodeling was significantly reduced with SHP2 inhibition.

Structured PICO

Does SHP2 inhibition improve ventricular remodeling by restoring AMPK phosphorylation and mitochondrial homeostasis in preclinical models of heart failure?

Population

Preclinical models of heart failure (Angiotensin II and Isoproterenol-induced ventricular remodeling)

Intervention

SHP2 inhibition (pharmacological with SHP099 or genetic with si-SHP2) and SHP2 overexpression/mutation

Comparator

Sham or vehicle control

Outcome

AMPK phosphorylation, mitochondrial homeostasis, and ventricular remodelingsurrogate

SHP2 directly dephosphorylates AMPK to trigger mitochondrial dysfunction, identifying SHP2 inhibition as a potential novel therapeutic strategy for heart failure.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

This study demonstrates that SHP2 acts as a key phosphatase directly dephosphorylates AMPK, thereby triggering mitochondrial dysfunction and exacerbating ventricular remodeling. Our findings provide novel mechanistic insights into heart failure progression and highlight SHP2 as a potential therapeutic target for heart failure treatment.

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