Throughout history, human circadian behavioral patterns have undergone significant shifts in their rhythms. Emerging evidence suggests that the intrinsic desynchronization of a person’s biological clock leads to exacerbated blood vessel dysfunction, the progression of atherosclerotic lesions, and an increased risk of atherosclerosis. However, the mechanisms that link disruptions in circadian clock to plaque vulnerability are not fully understood.
This study aims to elucidate the connection between personalized circadian molecular portraits and subsequent pathophysiological mechanisms, disease progression and remission, and other clinical manifestations. A total of 14 patients undergoing carotid endarterectomy were enrolled from Henan Province Clinical Research Center for Cardiovascular Diseases (CRCCD), providing 28 atherosclerotic plaques with which we conducted single-cell RNA sequencing for four advanced and four early lesion segment samples. Publicly available data included 3802 samples from 32 bulk cohorts and 24 samples from four single-cell cohorts. Using a systems biology approach, we deciphered transcriptomic drivers within the circadian system amidst atherosclerosis progression, gathering insights into the dynamic evolution of atherosclerosis under circadian influences. Developing an algorithm as a standardized quantification system provided a method for assessing and comparing endogenous atherosclerotic circadian clock misalignment profiles (ClockProAS) at high resolution, offering a comprehensive evaluation from clinical and biological perspectives.