Circadian rhythm gene cryptochrome 2 (Cry2) interacts with lipid metabolism to promote vascular aging.

Abstract

Background: Vascular aging is the basis of many chronic diseases of the aged, such as hypertension, coronary heart disease and stroke.

Objective: This study aims to deepen our understanding of the pathological mechanisms of vascular aging by combining multiple big data research methods, and reveal potential therapeutic targets and biomarkers.

Methods: WGCNA method was used to integrate the aortic transcriptome data of multiple age stages, and extract the key module and key pathway. The gene of aortic rhythm was integrated by JTK algorithm. Correlation calculation was performed for core gene and associated pathways. Finally, the expression of the core gene and their interaction with the associated pathways were verified in cell senescence.

Results: WGCNA showed that circadian rhythm is the key pathway of vascular aging, and circadian rhythm and metabolism interact to promote the occurrence of vascular aging. Cry2 has been identified as the most critical core rhythm gene. Lipid metabolism is the most Cry2-related subpathway, among which phospholipid metabolism and Serac1 have the strongest and most significant correlation with Cry2. Cry2 is mainly distributed in endothelial cells in both young and senescent blood vessels, and affects five lipid-related metabolic processes including lipid transport during endothelial senescence.

Conclusion: This study suggests that circadian rhythm and Cry2 may be potential targets of vascular aging, and further studies on their interaction with lipid metabolism will provide effective strategies for the prevention and treatment of age-related vascular diseases.