Circadian clock and cardiovascular disease.

Both the physiological and pathological functions of cardiovascular organs are closely related to circadian rhythm, an endogenously driven 24-h cycle. Heart rate, blood pressure, and endothelial function show diurnal variations within a day. The onset of cardiovascular disorders such as acute coronary syndrome, atrial arrhythmia, and subarachinoid hemorrhage also exhibits diurnal oscillation. Recent progress in studying the functions and molecular mechanisms of the biological clock brought forth the idea that intrinsic circadian rhythms are tightly related to cardiovascular pathology. The center of the biological clock exists in the suprachiasmatic nucleus in the hypothalamus. In addition to this central clock, each organ has its own biological clock system, termed the peripheral clock. Each cardiovascular tissue or cell, including heart and aortic tissue, cardiomyocyte, vascular smooth muscle cell, and vascular endothelial cell also has intrinsic biological rhythm. Until recently, little was known about the roles of peripheral clocks in cardiovascular organs. However, studies using genetically engineered mice revealed their contributions during the process of disease progression. Loss of synchronization between the internal clock and external stimuli can induce cardiovascular organ damage. Discrepancy in the phases between the central and peripheral clocks also seems to contribute to progression of the disorders. Elucidation of the precise roles of biological clocks in cardiovascular organs will provide us with more profound insights into the relevance of the circadian rhythm in cardiac pathology. Moreover, identification of the modalities with which we can manipulate the phase of each peripheral clock will enable us to establish a novel chronotherapeutic approach. This time-of-day based strategy may innovate a new paradigm in the prevention and treatment of cardiovascular disorders.