Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice

In this study, we first found that MyD88 expression was increased in cardiomyocytes of diabetic mouse hearts. In cultured cardiomyocytes, MyD88 inhibition either by siRNA or by small-molecular inhibitor LM8 markedly blocked TLR4-MyD88 complex formation, reduced pro-inflammatory mitogen-activated protein kinases/nuclear factor-κB (MAPKs/NF-κB) cascade activation and decreased pro-inflammatory cytokine expression under high glucose condition. Moreover, pharmacologic inhibition of MyD88 by LM8 showed significantly anti-inflammatory, anti-hypertrophic and anti-fibrotic effects in the hearts of both type 1 and type 2 diabetic mice. These beneficial effects of MyD88 inhibition were correlated to the reduced activation of TLR4-MyD88-MAPKs/NF-κB signaling pathways in the hearts. Taken together, MyD88 in cardiomyocytes mediates diabetes-induced cardiac inflammatory injuries and pharmacological inhibition of MyD88 shows significantly cardioprotective effects, indicating MyD88 as a potential therapeutic target for diabetic cardiomyopathy.PMID:36241098 | DOI:10.1016/j.bcp.2022.115292

Source: Biochemical Pharmacology - October 14, 2022 Category: Drugs & Pharmacology Authors: Wu Luo Gaojun Wu Xiaojun Chen Qiuyan Zhang Chunpeng Zou Jun Wang Jun Liu Nipon Chattipakorn Yi Wang Guang Liang Source Type: research