SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation
Authors' conclusion
Our findings revealed a key role of SNO-MLP in myocardial hypertrophy and demonstrated TLR3-mediated RIP3 and NLRP3 inflammasome activation as the downstream signaling pathway, which may represent a therapeutic target for myocardial hypertrophy and heart failure.
Study context
- Population
- Hypertrophic myocardium from patients, spontaneously hypertensive rats, TAC mice and neonatal rat cardiomyocytes
- Outcome
- Role of SNO-MLP in myocardial hypertrophy and its downstream mechanism under pressure overload
Main finding
As reported in the abstract
- SNO-MLP level significantly higher in hypertrophic myocardium from patients, spontaneously hypertensive rats and TAC mice
- SNO-MLP increased in angiotensin II- or phenylephrine-treated neonatal rat cardiomyocytes
- S-nitrosylated site of MLP identified at cysteine 79
- Mutation of cysteine 79 significantly reduced hypertrophic growth in treated cardiomyocytes and TAC mice
- Reducing SNO-MLP by S-nitrosoglutathione reductase overexpression greatly attenuated myocardial hypertrophy
- SNO-MLP stimulated TLR3 binding to MLP; downregulating TLR3 attenuated hypertrophy
- SNO-MLP increased TLR3–RIP3 complex formation, inducing NLRP3 inflammasome activation and promoting hypertrophy
Original publication
SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation. Circulation. Published 6 January 2020. doi:10.
Summarised from the published abstract; every number is checked against it