Key result
LKB1IP knockout protected mouse hearts against isoproterenol- or TAC-induced cardiac hypertrophy and fibrosis by targeting PTEN and activating Akt signalling.
Why the study?
Pathological cardiac hypertrophy is a leading cause of morbidity and mortality, but the role of LKB1IP in its development had not been explored.
Does LKB1IP knockout or inhibition prevent pathological cardiac hypertrophy in response to hypertrophic stimuli?
Does LKB1IP knockout or inhibition prevent pathological cardiac hypertrophy in response to hypertrophic stimuli?
Identifies LKB1IP as a novel therapeutic target for heart failure;.
Pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide. Liver kinase B1 interacting protein 1 (LKB1IP) was identified as the binding protein of tumour suppressor LKB1. However, the role of LKB1IP in the development of pathological cardiac hypertrophy has not been explored. The aim of this study was to investigate the function of LKB1IP in cardiac hypertrophy in response to hypertrophic stimuli. We investigated the cardiac level of LKB1IP in samples from patients with heart failure and mice with cardiac hypertrophy induced by isoproterenol (ISO) or transverse aortic constriction (TAC). LKB1IP knockout mice were generated and challenged with ISO injection or TAC surgery. Cardiac function, hypertrophy and fibrosis were then examined. LKB1IP expression was significantly up-regulated on hypertrophic stimuli in both human and mouse cardiac samples. LKB1IP knockout markedly protected mouse hearts against ISO- or TAC-induced cardiac hypertrophy and fibrosis. LKB1IP overexpression aggravated ISO-induced cardiomyocyte hypertrophy, and its inhibition attenuated hypertrophy in vitro. Mechanistically, LKB1IP activated Akt signalling by directly targeting PTEN and then inhibiting its phosphatase activity. In conclusion, LKB1IP may be a potential target for pathological cardiac hypertrophy.
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Tian et al. (2021) studied Pathological cardiac hypertrophy. LKB1IP knockout vs. Wild-type/control was evaluated on Cardiac hypertrophy and fibrosis. LKB1IP knockout protected mouse hearts against isoproterenol- or TAC-induced cardiac hypertrophy and fibrosis by targeting PTEN and activating Akt signalling.
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