Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease.

Area of Science:

• Cardiovascular biology
• Chronobiology
• Metabolic disorders

Background:

• Hypercholesterolemia is a significant risk factor for cardiovascular diseases.
• Circadian rhythm abnormalities are increasingly recognized as contributing to various health issues.

Purpose of the Study:

• To investigate the impact of hypercholesterolemia on circadian rhythms.
• To explore the combined effects of hypercholesterolemia and circadian dysfunction on cardiovascular disease progression.

Main Methods:

• Utilized low-density lipoprotein receptor (LDLR)-deficient mice as a model for familial hypercholesterolemia.
• Assessed circadian behavior in constant darkness and under light-dark cycles.
• Generated double-mutant mice with LDLR deficiency and a Period2 mutation to impair circadian rhythms.
• Quantified artery plaque area and inflammatory cytokine levels (IL-6).

Main Results:

• LDLR-deficient mice displayed prolonged active phases and bimodal rhythms in constant darkness.
• Even when entrained, these mice showed reduced behavioral onset intensity.
• Double-mutant mice exhibited significantly enlarged artery plaque areas.
• Elevated levels of the inflammatory cytokine IL-6 were observed in double-mutant mice.

Conclusions:

• Hypercholesterolemia, modeled by LDLR deficiency, is associated with circadian abnormalities.
• The combination of hypercholesterolemia and impaired circadian rhythms exacerbates cardiovascular disease progression.
• Circadian dysfunction may play a role in the development and advancement of cardiovascular diseases.