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

## TL;DR

TIGAR deficiency reduces cardiac hypertrophy in mice with Ang-II-induced hypertension, despite similar blood pressure and systolic function.

## Contribution

This study reveals a novel role of TIGAR in regulating glucose metabolism during Ang-II-induced cardiac hypertrophy.

## Key findings

- TIGAR knockout mice showed reduced cardiac hypertrophy despite similar blood pressure and systolic dysfunction.
- TIGAR deficiency was associated with increased levels of fructose 2,6-bisphosphate, PFK-1, and Glut-4.
- Ang-II induced similar diastolic dysfunction in both wild-type and TIGAR knockout mice.

## Abstract

Hypertension is the key contributor to pathological cardiac hypertrophy. Growing evidence indicates that glucose metabolism plays an essential role in cardiac hypertrophy. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glucose metabolism in pressure overload-induced cardiac remodeling. In the present study, we investigated the role of TIGAR in cardiac remodeling during Angiotensin II (Ang-II)-induced hypertension. Wild-type (WT) and TIGAR knockout (KO) mice were infused with Angiotensin-II (Ang-II, 1 µg/kg/min) via mini-pump for four weeks. The blood pressure was similar between the WT and TIGAR KO mice. The Ang-II infusion resulted in a similar reduction of systolic function in both groups, as evidenced by the comparable decrease in LV ejection fraction and fractional shortening. The Ang-II infusion also increased the isovolumic relaxation time and myocardial performance index to the same extent in WT and TIGAR KO mice, suggesting the development of similar diastolic dysfunction. However, the knockout of TIGAR significantly attenuated hypertension-induced cardiac hypertrophy. This was associated with higher levels of fructose 2,6-bisphosphate, PFK-1, and Glut-4 in the TIGAR KO mice. Our present study suggests that TIGAR is involved in the control of glucose metabolism and glucose transporters by Ang-II and that knockout of TIGAR attenuates the development of maladaptive cardiac hypertrophy.