Fibronectin synthesis by aorta explants from rabbits fed high cholesterol diets

Area of Science:

• Biochemistry
• Cell Biology
• Cardiovascular Research

Background:

• Atherogenesis involves complex changes in the arterial extracellular matrix.
• Fibronectin is a key glycoprotein in the extracellular matrix, crucial for cell adhesion and matrix assembly.
• Dietary factors, such as high fat and cholesterol, are known contributors to cardiovascular disease progression.

Purpose of the Study:

• To investigate the impact of a high-fat, high-cholesterol diet on fibronectin synthesis and secretion in rabbit aorta explants.
• To determine if dietary-induced hypercholesterolemia alters the glycosylation of newly synthesized fibronectin.

Main Methods:

• Rabbit aorta explants were cultured after feeding a high-fat, high-cholesterol diet or a control diet.
• Fibronectin synthesis was assessed using radiolabeling with [14C]leucine (protein core) and [3H]mannose (oligosaccharide chains).
• Immunoprecipitation with anti-fibronectin antibody and analysis by gel filtration, heparin-Sepharose, and gelatin-Sepharose chromatography were employed.

Main Results:

• Fibronectin synthesis, measured by [14C]leucine incorporation, increased by 81% in explants from hypercholesterolemic rabbits.
• [3H]Mannose incorporation into fibronectin was significantly altered, indicating changes in glycosylation.
• Pulse-chase experiments revealed increased fibronectin secretion and altered glycosylation patterns in aorta explants from cholesterol-fed rabbits.

Conclusions:

• High fat-cholesterol intake alters fibronectin synthesis and glycosylation in rabbit aorta explants.
• These alterations in fibronectin composition suggest a potential mechanism for matrix dysfunction during atherogenesis.
• Dietary-induced changes in glycoprotein synthesis may play a causative role in the development of cardiovascular disease.