| First Author | Liu L | Year | 2023 |
| Journal | Int J Biol Sci | Volume | 19 |
| Issue | 11 | Pages | 3428-3440 |
| PubMed ID | 37497006 | Mgi Jnum | J:338563 |
| Mgi Id | MGI:7513299 | Doi | 10.7150/ijbs.84426 |
| Citation | Liu L, et al. (2023) Lats2 deficiency protects the heart against myocardial infarction by reducing inflammation and inhibiting mitochondrial fission and STING/p65 signaling. Int J Biol Sci 19(11):3428-3440 |
| abstractText | Large tumor suppressor kinase 2 (Lats2) is a member of the Hippo pathway, a critical regulator of organ size. Since Lats2 activity may trigger mitochondrial dysfunction, a key pathogenic factor in acute myocardial infarction (AMI), this study sought to investigate whether Lats2 deletion confers cardioprotection in AMI. AMI was induced in cardiomyocyte-specific Lats2 knockout (Lats2(Cko)) and control (Lats2(flox)) mice. Twenty-eight days after AMI surgery, myocardial performance and mitochondrial homeostasis were impaired in Lats2(flox)mice. In contrast, Lats2(Cko) mice exhibited markedly preserved cardiac structure and contraction/relaxation activity, decreased fibrosis, reduced circulating cardiac injury biomarker levels, and enhanced cardiomyocyte viability. Consistent with these findings, siRNA-mediated Lats2 silencing sustained mitochondrial respiration and inhibited apoptosis in hypoxia-treated HL-1 cardiomyocytes. Notably, Lats2 deficiency inhibited AMI/hypoxia-related mitochondrial fission and inactivated STING/p65 signaling by preventing hypoxia-induced release of mtDNA into the cytosol. Accordingly, pharmacological reactivation of STING signaling abolished the cardioprotective effects of Lats2 ablation. Those data suggest that AMI-induced Lats2 upregulation is associated with impaired cardiomyocyte viability and function resulting from enhanced mitochondrial fission, mtDNA release, and STING/p65 pathway activation. |
