Nuclear Receptors and Clock Components in Cardiovascular Diseases

Area of Science:

• Cardiovascular research
• Chronobiology
• Molecular medicine

Background:

• Cardiovascular diseases (CVD) remain the leading global cause of mortality, primarily driven by atherosclerotic plaque development.
• Factors contributing to atherosclerosis include traditional risk factors and recently identified circadian rhythm disruption, particularly in shift workers.
• Nuclear receptors, including Rev-erb and ROR, regulate metabolism, inflammation, and the biological clock, presenting potential therapeutic targets.

Purpose of the Study:

• To explore the therapeutic potential of targeting nuclear receptors involved in the biological clock for treating atherosclerosis.
• To investigate the efficacy of chronotherapy in managing cardiovascular disease progression.
• To review the role of Rev-erb and ROR nuclear receptors in metabolic and inflammatory pathways relevant to CVD.

Main Methods:

• Review of current literature on atherosclerosis, circadian rhythms, and nuclear receptor function.
• Analysis of preclinical studies demonstrating the efficacy of chronotherapy in reducing atherosclerotic plaque progression in mouse models.
• Discussion of the mechanisms by which Rev-erb and ROR nuclear receptors influence metabolic homeostasis and inflammation.

Main Results:

• Chronotherapy has demonstrated efficacy in reducing plaque progression in preclinical models without affecting healthy tissues.
• Targeting ligand-activated core clock components offers a potential strategy for managing atherosclerosis.
• Rev-erb and ROR nuclear receptors are key regulators of metabolic and inflammatory processes implicated in CVD.

Conclusions:

• Targeting nuclear receptors like Rev-erbs and RORs within a chronotherapeutic framework presents a promising strategy for treating cardiovascular diseases.
• This approach may offer a way to dampen atherosclerosis progression while minimizing drug-related side effects.
• Further research into the precise mechanisms and clinical application of chronotherapy for CVD is warranted.