HF and Intensive Care: Editorial Comment
Cardiology 2020;145:356–358
No Time to Die: Can We Fix a Broken
Cardiovascular Clock?
Simon Matskeplishvili Alexander Kalinkin
Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russia
Received: February 17, 2020
Accepted: February 24, 2020
Published online: April 29, 2020
Simon Matskeplishvili, MD, PhD
Medical Research and Education Center, Lomonosov Moscow State University
27/10 Lomonosovsky prospect
Moscow 119234 (Russia)
simonmats @yahoo.com
© 2020 S. Karger AG, Basel karger@karger.com
www.karger.com/crd
DOI: 10.1159/000506730
Circadian (from Latin circā diēm – around a day)
rhythms (CR) – the biological oscillations based upon our
built-in diurnal clock – have a profound effect on human
physiology and cellular functions. A master clock in the
suprachiasmatic nucleus of the hypothalamus, or SCN,
coordinates and synchronizes all the biological clocks in
a living organism [1].
Historically, the first research of CRs was published in
1729 by a French astronomer Jean Jacques d’Ortous de
Mairan [2]. He experimented with plants and sleep cycles
and observed that the daily opening and closing of the
leaves of a heliotrope plant in a dark room occurred with-
out any exposure to sunlight. This proved that plants had
intrinsic CR working regardless of lighting conditions.
For quite a long time, it was not clear whether the CR
existed as a response to the external stimuli or whether
there was an endogenous trigger behind physiological
changes. It took many years of research until the Nobel
Prize for Medicine in 2017 was awarded to Michael
Young, Michael Rosbash and Jeffrey Hall for their discov-
eries of molecular mechanisms controlling the CR [3].
Genome-wide transcriptome, metabolome and proteome
studies have significantly improved our understanding of
the circadian regulation. In addition to the central clock,
many fundamental “housekeeping” mechanisms were
identified in different tissues.
Importantly, disorders of human biological clocks in-
crease the risk of disease. These disturbances can arise
from various sources and are important to identify as they
can cause serious dysfunction in major internal systems
or even increase the probability of many diseases includ-
ing depression, stroke and cancer.
CRs continuously control our cardiovascular system
through gene and protein manipulation resulting in the
diurnal variation of cardiovascular events [4]. In the
morning, heart rate, blood pressure, platelet reactivity,
vasoconstriction and intra-arterial pressures increase af-
ter the night-time dip, coupled with endothelial dysfunc-
tion and decreased fibrinolysis. This leads to increased
vulnerability of the cardiovascular system leading to acute
cardiac events, such as sudden cardiac death, acute coro-
nary syndrome, stroke, and ventricular arrhythmias [5].
The first analysis of such a relationship was performed
by Schneider [6] in 1859 who investigated time and cause
of death in 114,183 people who died in Berlin between
January 1847 and December 1857. Only 126 years later,
Muller et al. [7] published the first study on circadian
variation of the incidence of cardiovascular events. Au-