Abstract
A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.
Highlights
Atrial fibrillation (AF) is one of the most common cardiovascular diseases in patients, and it increases the risk of embolic stroke, heart failure, and mortality compared to patients without atrial fibrillation (AF) [1]
The results showed mRNA expression of CRY1 [Standardized β coefficient = 0.386, p = 0.041], NR1D1 [Standardized β coefficient = 1.149, p = 0.016], RORA [β = −1.676, p = 0.025], and left atrial (LA) volume [Standardized β coefficient = 0.608, p < 0.001] were significantly associated with the atrial high-rate episodes (AHREs) burden (R2 = 0.633; p < 0.001) (Table 3)
Our study revealed that the expression of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM was associated with AHRE burden, which implies that other circadian clock genes may play an important role in the variability of heart rate change, and in the development of AF
Summary
Atrial fibrillation (AF) is one of the most common cardiovascular diseases in patients, and it increases the risk of embolic stroke, heart failure, and mortality compared to patients without AF [1]. According to a previous study, a prominent circadian variation is present in AF episodes in patients with paroxysmal AF [2]. Circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms. A major feature of circadian rhythm is that the mRNA and protein of the circadian clock genes and the mRNA and protein of the genes regulated by circadian rhythm exhibit distinct daily day–night fluctuation cycles [3,4]. Some cardiovascular or metabolic diseases, such as hypertension and diabetes, have been shown to be involved in the regulation of physiological clock genes [5]. The onset of acute myocardial infarction and arrhythmias is regulated by circadian clock genes [6].
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