Rudic R Daniel, McNamara Peter, Reilly Dermot, Grosser Tilo, Curtis Anne-Marie, Price Thomas S, Panda Satchidananda, Hogenesch John B, FitzGerald Garret A
The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Circulation. 2005 Oct 25;112(17):2716-24. doi: 10.1161/CIRCULATIONAHA.105.568626. Epub 2005 Oct 17.
Circadian rhythmicity of many aspects of cardiovascular function-blood pressure, coagulation and contractile function-is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta.
Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression was assessed by expression profiling and subjected to a gene ontology bioinformatics analysis. Three hundred thirty transcripts exhibited a circadian pattern of oscillation in mouse aorta, including those intrinsic to the function of the molecular clock. In addition, many genes relevant to protein folding, protein degradation, glucose and lipid metabolism, adipocyte maturation, vascular integrity, and the response to injury are also included in this subset of roughly 7000 genes screened for circadian oscillation.
Detection of functional cassettes of vascular genes that exhibit circadian regulation in the mouse will facilitate elucidation of the mechanisms by which the molecular clock may interact with environmental variables to modulate cardiovascular function and the response to therapeutic interventions.
心血管功能的许多方面——血压、凝血和收缩功能——都有明确的昼夜节律，重要临床事件如心肌梗死和中风也存在日变化。在此，我们开展研究以全面评估小鼠主动脉中的昼夜节律基因表达。
在两个昼夜周期（48小时）内，每隔4小时采集小鼠的主动脉。通过表达谱评估基因表达，并进行基因本体生物信息学分析。330个转录本在小鼠主动脉中呈现昼夜振荡模式，包括分子钟功能所固有的那些转录本。此外，在筛选的约7000个基因子集中，还包括许多与蛋白质折叠、蛋白质降解、葡萄糖和脂质代谢、脂肪细胞成熟、血管完整性以及损伤反应相关的基因。
检测小鼠中表现出昼夜调节的血管基因功能盒，将有助于阐明分子钟与环境变量相互作用以调节心血管功能及对治疗干预反应的机制。
