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Updated: Jan 8, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
L-GILZ is essential for cardiac function and protects against pressure overload-induced hypertrophy and dysfunction
Hai Ying Fu1, Miki Imazu2, Shin Ito2
1Department of Biochemistry, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Objective:
Glucocorticoid-induced leucine zipper (GILZ) deficiency has been shown to exacerbate angiotensin-induced cardiomyocyte hypertrophy and diastolic dysfunction. However, the specific role of the long isoform of GILZ (L-GILZ) in cardiac function remains unclear. This study aimed to investigate the role of L-GILZ in maintaining cardiac function and its protective effects against pressure overload-induced hypertrophy and dysfunction.
Methods:
Institute of Cancer Research mice were used in this study. The human L-GILZ gene or short hairpin RNA targeting mouse L-GILZ was introduced via adeno-associated virus 9 under the control of the cardiac troponin-T promoter, ensuring cardiac-specific overexpression or knockdown. Luciferase and short hairpin RNA targeting LacZ served as respective controls. L-GILZ expression was analyzed by western blot analysis and real-time polymerase chain reaction, while extracellular signal-regulated kinase (ERK) phosphorylation was assessed via western blot analysis. RNA sequencing was performed to evaluate gene expression changes following L-GILZ knockdown. Pressure overload was induced by transverse aortic constriction (TAC), and echocardiography was used to assess cardiac function.
Results:
TAC-induced pressure overload reduced L-GILZ expression but not GILZ expression. Cardiac-specific overexpression of human L-GILZ was successfully achieved in mouse hearts, with no detectable expression in other organs. L-GILZ overexpression significantly attenuated TAC-induced cardiac hypertrophy, dysfunction, and ERK phosphorylation. Conversely, L-GILZ knockdown led to hypertrophy, cardiac dysfunction, and enhanced ERK phosphorylation. RNA sequencing revealed that L-GILZ knockdown reduced the expression of mitochondria-associated genes, including cytochrome c oxidase, adenosine triphosphate synthase, and mitochondrial nicotinamide adenine dinucleotide (reduced form) dehydrogenase.
Conclusion:
L-GILZ plays a critical role in maintaining cardiac function and homeostasis. Cardiac-specific overexpression of L-GILZ may serve as a potential therapeutic strategy for preventing and treating cardiac hypertrophy and heart failure.
