7-Ketocholesterol Induces Lipid Metabolic Reprogramming and Enhances Cholesterol Ester Accumulation in Cardiac Cells

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Metabolomics

Background:

• 7-Ketocholesterol (7KCh) is a key oxidized cholesterol product found in atherosclerotic plaques.
• Previous research indicated 7KCh accumulation in erythrocytes of heart failure patients.

Purpose of the Study:

• To investigate the metabolic effects of 7KCh on cardiomyocytes.
• To elucidate the molecular mechanisms underlying 7KCh-induced metabolic changes in cardiac cells.

Main Methods:

• Metabolomic analysis of HL-1 cardiac cells treated with 7KCh.
• mRNA sequencing (mRNA-seq) to analyze gene expression changes in response to 7KCh.
• Integrated analysis of metabolomic and transcriptomic data.

Main Results:

• 7KCh treatment led to decreased levels of mevalonic acid (MVA) pathway metabolites, phospholipids, and triacylglycerols.
• Lysophospholipid levels, including lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), significantly increased.
• Cholesteryl ester production was enhanced, with differential gene expression observed in lipid metabolism, MVA biosynthesis, and cholesterol esterification pathways.

Conclusions:

• 7KCh induces significant reprogramming of lipid metabolism in cardiac cells.
• Altered transcription of genes involved in lipid metabolism, such as sterol O-acyltransferase and phospholipase A2, contributes to cholesteryl ester accumulation.
• These 7KCh-induced metabolic alterations in cardiac cells may play a role in the pathogenesis of cardiovascular diseases.