The vascular clock system generates the intrinsic circadian rhythm of vascular contractility

Area of Science:

• Cardiovascular biology
• Chronobiology
• Molecular medicine

Background:

• Cardiovascular parameters and coronary artery disease incidence exhibit circadian variations.
• Diurnal changes in vascular contractility are suspected to underlie these day/night variances.
• The molecular mechanisms of the vascular clock system generating these variations remain largely unknown.

Purpose of the Study:

• To investigate the molecular basis of the intrinsic circadian rhythm in vascular contractility.
• To elucidate the role of clock genes in regulating vascular smooth muscle cell (VSMC) function.
• To review recent findings on the biological clock system and cardiovascular chronobiology.

Main Methods:

• Identification of intrinsic circadian rhythm in vascular contractility.
• Analysis of clock gene expression in vascular smooth muscle cells (VSMC).
• Investigation of Rho-associated kinase 2 (ROCK2) expression and its regulation by clock genes.

Main Results:

• A clock gene, Rorα, in VSMCs provokes diurnal oscillations in Rho-associated kinase 2 (ROCK2) expression.
• ROCK2 expression changes induce time-of-day-dependent variations in agonist-induced myosin light chain (MLC) phosphorylation.
• These molecular events lead to variations in myofilament Ca(2+) sensitization.

Conclusions:

• The Rorα/ROCK2 pathway in VSMCs is a key molecular mechanism underlying vascular circadian rhythms.
• This pathway contributes to the time-of-day-dependent regulation of vascular contractility.
• Understanding this vascular clock system offers insights into cardiovascular chronobiology and disease.