Molecular time: an often overlooked dimension to cardiovascular disease

Diurnal rhythms influence cardiovascular physiology such as heart rate and blood pressure and the incidence of adverse cardiac events such as heart attack and stroke. For example, shift workers and patients with sleep disturbances, such as obstructive sleep apnea, have an increased risk of heart attack, stroke, and sudden death. Diurnal variation is also evident at the molecular level, as gene expression in the heart and blood vessels is remarkably different in the day as compared to the night. Much of the evidence presented here indicates that growth and renewal (structural remodeling) are highly dependent on processes that occur during the subjective night. Myocardial metabolism is also dynamic with substrate preference also differing day from night. The risk/benefit ratio of some therapeutic strategies and the appearance of biomarkers also vary across the 24-hour diurnal cycle. Synchrony between external and internal diurnal rhythms and harmony among the molecular rhythms within the cell is essential for normal organ biology. Cell physiology is 4 dimensional; the substrate and enzymatic components of a given metabolic pathway must be present not only in the right compartmental space within the cell but also at the right time. As a corollary, we show disrupting this integral relationship has devastating effects on cardiovascular, renal and possibly other organ systems. Harmony between our biology and our environment is vital to good health.