High dietary methionine plus cholesterol stimulates early atherosclerosis and late fibrous cap development which is...

Area of Science:

• Cardiovascular Science
• Nutritional Science
• Cellular Biology

Background:

• The role of homocysteine and methionine in fibrous cap formation and endoplasmic reticulum (ER) stress is not fully understood.
• Homocysteine is known to promote collagen accumulation and upregulate the ER stress marker GRP78.
• Investigating dietary methionine's impact on atherosclerosis and ER stress is crucial for understanding plaque development and stability.

Purpose of the Study:

• To investigate if high dietary methionine intake increases fibrous cap formation in atherosclerotic plaques.
• To determine if transitioning to a normal diet reduces ER stress markers in existing plaques.
• To explore the relationship between dietary methionine, plaque composition, and ER stress in an animal model.

Main Methods:

• New Zealand white rabbits were fed atherogenic diets with varying methionine and cholesterol levels for different durations.
• Plaque regression was studied by feeding an atherogenic diet followed by a normal diet.
• Endothelial function, atherosclerosis progression, and the presence of GRP78-positive cells were quantified.

Main Results:

• High methionine and cholesterol diet significantly increased atherosclerosis and fibrous cap formation compared to cholesterol alone.
• While high methionine diets increased fibrous caps, they showed reduced GRP78 expression compared to cholesterol-only diets.
• Dietary methionine withdrawal led to decreased GRP78-positive cells, suggesting reduced ER stress and plaque stabilization.

Conclusions:

• High dietary methionine may promote plaque stabilization by increasing fibrous cap thickness.
• A normal diet facilitates plaque stabilization and reduces cellular ER stress.
• Dietary interventions involving methionine and cholesterol warrant further investigation for cardiovascular health.