Endothelial CD36 mediates diet-induced increases in aortic stiffness

Area of Science:

• Cardiovascular Biology
• Metabolic Diseases
• Molecular Medicine

Background:

• Western diets (WD) are linked to obesity, insulin resistance, and arterial stiffening, major cardiovascular disease risk factors.
• Elevated CD36 expression correlates with ectopic lipid accumulation, insulin resistance, and arterial stiffening.
• Endothelial cell-specific CD36 (ECCD36) role in WD-induced vascular dysfunction remains unclear.

Purpose of the Study:

• To investigate the role of endothelial cell-specific CD36 (ECCD36) in Western diet-induced aortic insulin resistance, lipid accumulation, inflammation, fibrosis, remodeling, and stiffening.

Main Methods:

• Female ECCD36 knockout and wild-type mice were fed WD or standard chow for 16 weeks.
• Aortic stiffness assessed by pulse wave velocity; vascular function by wire myography.
• Gene expression, lipid content, and aortic remodeling analyzed using molecular and histological techniques.

Main Results:

• WD induced aortic stiffening, insulin resistance, and impaired insulin signaling (PI3K/Akt pathway).
• WD-associated changes included mTOR/S6K activation, lipid dysregulation, reduced occludin, inflammation, and remodeling.
• These WD-induced abnormalities were significantly attenuated in ECCD36 knockout mice.

Conclusions:

• Heightened ECCD36 signaling under WD contributes to aortic insulin resistance, lipid accumulation, and endothelial dysfunction.
• ECCD36 promotes inflammation, fibrosis, vascular remodeling, and arterial stiffening in response to a Western diet.
• Targeting ECCD36 may offer a therapeutic strategy against diet-induced cardiovascular complications.