Abstract
BackgroundAcute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs.MethodsFifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors’ normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).ResultsAfter serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbα mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed.ConclusionThe present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque.
Highlights
Acute myocardial infarction and stroke are more likely to occur in the early morning
This system includes the central circadian clock residing in the hypothalamic suprachiasmatic nucleus (SCN) [1] and the peripheral clock located in many peripheral tissues
vascular smooth muscle cells (VSMCs) cultured from normal carotid had a typical fusiform shape, while cells cultured from plaques had two distinctly different morphologies: fusiform and a big, flattened shape (Figure 1C and D)
Summary
Acute myocardial infarction and stroke are more likely to occur in the early morning. Many behavioral and physiological processes exhibit circadian (approximately 24 h) rhythms that are controlled by a clock system This system includes the central circadian clock residing in the hypothalamic suprachiasmatic nucleus (SCN) [1] and the peripheral clock located in many peripheral tissues. Acute myocardial infarction and stroke, severe complications resulted from atherosclerosis, are more likely to occur in the early morning [5,6]. Epidemiological studies have indicated that shift workers suffer from a higher risk of atherosclerosis and cardiovascular events [7]. These phenomena cannot be explained by the change in blood pressure and platelet function [8]. Previous animal research has already illustrated that the disruption of circadian rhythms could impair vessels and enhance atherosclerosis [9,10]
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