Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice

Area of Science:

• Cardiovascular Science
• Metabolic Research
• Evolutionary Biology

Background:

• Lipoprotein(a) (Lp(a)) is a significant risk factor for cardiovascular disease, prevalent in humans and primates but rare in other mammals.
• Understanding Lp(a)'s evolutionary role may clarify its physiological function.
• A mouse model mimicking human metabolism (Lp(a) expression, no endogenous vitamin C) was developed.

Purpose of the Study:

• To investigate the relationship between ascorbate (vitamin C) levels and Lipoprotein(a) (Lp(a)).
• To explore the impact of ascorbate deficiency on Lp(a) metabolism and vascular health.
• To elucidate the physiological role of Lp(a) in the context of vitamin C deficiency.

Main Methods:

• Developed a novel mouse model expressing human Lipoprotein(a) and lacking endogenous ascorbate production.
• Administered dietary ascorbate deficiency, including chronic hypoascorbemia and complete depletion (scurvy).
• Monitored serum Lp(a) levels and Lp(a) deposition in the vascular wall.

Main Results:

• Dietary ascorbate deficiency was shown to increase serum Lp(a) levels.
• Chronic and severe ascorbate deficiency led to Lp(a) accumulation within the vascular wall.
• Lp(a) accumulation paralleled the development of atherosclerotic lesions in ascorbate-deficient mice.

Conclusions:

• Dietary ascorbate deficiency emerges as an independent risk factor for atherosclerosis, separate from dietary lipids.
• Lp(a) may function as a mobile repair molecule, addressing vascular wall damage.
• This study supports the role of Lp(a) in compensating for structural impairments associated with hypoascorbemia and scurvy.