Cholesterol induces cardiac hypertrophy by activating the AKT pathway

Area of Science:

• Cardiology
• Molecular Biology
• Cell Biology

Background:

• Cardiac hypertrophy is a significant risk factor for heart failure and sudden death.
• The direct role of cholesterol in inducing cardiac hypertrophy remains unclear.
• Understanding cholesterol's impact on cardiac cells is crucial for cardiovascular disease research.

Purpose of the Study:

• To investigate if cholesterol alone can induce cardiac hypertrophy.
• To identify the cellular mechanisms involved in cholesterol-induced cardiac hypertrophy.
• To utilize H9c2 cells as a model system for studying these cellular responses.

Main Methods:

• Cholesterol loading of H9c2 cells.
• Measurement of cellular surface area.
• Analysis of hypertrophy marker gene expression (β-myosin-heavy chain).
• Investigation of signaling pathway activation (ERK/MAPK, PI3K/AKT).
• Pharmacological inhibition of the PI3K/AKT pathway using LY294002.

Main Results:

• Cholesterol loading significantly increased H9c2 cell surface area.
• Cholesterol loading upregulated the expression of the cardiac hypertrophy marker gene β-myosin-heavy chain (β-MHC).
• Cholesterol activated both the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathways.
• Inhibition of the PI3K/AKT pathway with LY294002 markedly reduced cholesterol-induced increases in cell surface area and β-MHC mRNA expression.

Conclusions:

• Cholesterol can directly induce cardiac hypertrophy in H9c2 cells.
• The PI3K/AKT signaling pathway plays a critical role in mediating cholesterol-induced cardiac hypertrophy.
• These findings suggest cholesterol is a key factor in the development of cardiac hypertrophy, potentially via PI3K/AKT activation.