TIGAR Deficiency Blunts Angiotensin-II-Induced Cardiac Hypertrophy in Mice

Area of Science:

• Cardiovascular Biology
• Metabolic Regulation
• Molecular Cardiology

Background:

• Hypertension is a primary driver of pathological cardiac hypertrophy.
• Glucose metabolism is increasingly recognized for its critical role in cardiac hypertrophy.
• TP53-induced glycolysis and apoptosis regulator (TIGAR) influences glucose metabolism in cardiac remodeling.

Purpose of the Study:

• To investigate the role of TIGAR in cardiac remodeling during Angiotensin II (Ang-II)-induced hypertension.
• To determine if TIGAR deficiency impacts Ang-II-induced cardiac hypertrophy and associated metabolic changes.

Main Methods:

• Wild-type (WT) and TIGAR knockout (KO) mice were subjected to Angiotensin-II (Ang-II) infusion for four weeks.
• Cardiac function (systolic and diastolic) was assessed using echocardiography.
• Cardiac hypertrophy, glucose metabolism markers (fructose 2,6-bisphosphate, PFK-1, Glut-4), and blood pressure were analyzed.

Main Results:

• Ang-II infusion induced similar systolic and diastolic dysfunction in both WT and TIGAR KO mice.
• TIGAR knockout significantly attenuated Ang-II-induced cardiac hypertrophy compared to WT mice.
• TIGAR KO mice exhibited higher levels of fructose 2,6-bisphosphate, PFK-1, and Glut-4.

Conclusions:

• TIGAR is implicated in Ang-II-mediated regulation of glucose metabolism and glucose transporters in the heart.
• TIGAR deficiency mitigates maladaptive cardiac hypertrophy in response to Ang-II-induced hypertension.
• Targeting TIGAR may offer a therapeutic strategy for preventing hypertensive cardiac remodeling.