Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice.

Area of Science:

• Cardiovascular Research
• Nutritional Science
• Biochemistry

Background:

• Calcific aortic valve disease (CAVD) involves progressive aortic valve calcification, leading to dysfunction.
• Risk factors for CAVD include aging and dyslipidemia.
• Vitamin K has shown potential in inhibiting vascular and valvular calcification.

Purpose of the Study:

• To investigate the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification.
• To assess MK4's impact in a hypercholesterolemic mouse model of CAVD.

Main Methods:

• LDLr-/-ApoB100/100 male mice were fed a Western diet for 5 months.
• Mice received either a standard Western diet or one supplemented with 0.2 mg/g MK4.
• Evaluated body weight, aortic valve and liver morphology (immunohistochemistry), plasma cholesterol, hepatic cytokines, and hepatic gene expression.

Main Results:

• MK4 supplementation exacerbated the lipoprotein lipid profile, increasing plasma LDL and triglycerides.
• The MK4-containing diet led to increased hepatic steatosis and upregulated genes for triglyceride and cholesterol synthesis.
• MK4 reduced liver levels of inflammatory cytokines like IL-6, TNFα, and MCP1.

Conclusions:

• MK4 did not improve aortic valve morphology in this hypercholesterolemic mouse model.
• MK4 may have detrimental effects on circulating lipid levels, particularly in hypercholesterolemic individuals.
• Further research is needed to clarify Vitamin K2's role in cardiovascular health and calcific aortic valve disease.