Palmitic acid induces cardiomyocyte apoptosis by enhancing the KLF4/cMLCK signaling pathway

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Apoptosis

Background:

• Cardiovascular diseases, driven by hyperlipidemia and myocardial apoptosis, are leading causes of mortality.
• Krüppel-like factor 4 (KLF4) is implicated in cardiac myocyte apoptosis under stress.
• Palmitic acid (PA) induces cardiac myocyte apoptosis, but the underlying mechanisms involving KLF4 are not fully understood.

Purpose of the Study:

• To investigate the role and mechanism of Krüppel-like factor 4 (KLF4) in palmitic acid (PA)-induced cardiac myocyte apoptosis.
• To explore the potential synergistic interaction between KLF4 and cardiac myosin light-chain kinase (cMLCK) in lipotoxicity-induced apoptosis.
• To identify novel therapeutic targets for cardiovascular disease treatment.

Main Methods:

• Utilized in vitro and in vivo models of lipotoxicity using palmitic acid (PA).
• Investigated the expression levels of KLF4 and cMLCK under PA influence.
• Employed selective knockdown and overexpression of KLF4 and cMLCK in cardiomyocytes.

Main Results:

• Palmitic acid (PA) exposure led to increased KLF4 expression and decreased cMLCK expression in cardiomyocytes.
• KLF4 upregulation correlated with cardiomyocyte apoptosis and inhibited cell proliferation.
• Overexpression of cMLCK attenuated PA-induced cardiac myocyte apoptosis, while KLF4 knockdown confirmed its pro-apoptotic role.

Conclusions:

• KLF4 exhibits a pro-apoptotic effect in PA-induced cardiac myocyte apoptosis.
• The KLF4/cMLCK signaling pathway plays a critical role in PA-induced cardiac myocyte apoptosis and cell proliferation inhibition.
• This study highlights the KLF4/cMLCK pathway as a potential therapeutic target for cardiovascular diseases.