The role of clock genes and circadian rhythm in the development of cardiovascular diseases

2015 ◽  
Vol 72 (17) ◽  
pp. 3225-3234 ◽  
Author(s):  
Norihiko Takeda ◽  
Koji Maemura
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Clock Genes

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

2019 ◽  
Vol 8 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Shuhui Ma ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Clock Genes ◽  
Critical Role ◽  
Green Light ◽  
Circadian Oscillator ◽  
Melatonin Secretion ◽  
Expression Levels

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin.

Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats

2007 ◽  
Vol 293 (5) ◽  
pp. E1325-E1334 ◽  
Author(s):  
Maristela O. Poletini ◽  
De'Nise T. McKee ◽  
Jessica E. Kennett ◽  
Jamie Doster ◽  
Marc E. Freeman
Keyword(s):  
Circadian Rhythm ◽  
Locus Coeruleus ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Random Sequence ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Gene Expressions ◽  
Circadian Time

The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor output cycles kaput ( Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes ( Per1, Per2, and Clock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity.

scholarly journals The role of circadian clock genes in mental disorders

2007 ◽  
Vol 9 (3) ◽  
pp. 333-342 ◽  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Psychiatric Disorders ◽  
Rem Sleep ◽  
Seasonal Affective Disorder ◽  
Clock Genes ◽  
Sleep Latency ◽  
Sleep Efficiency ◽  
Circadian Clock Genes

The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain.

scholarly journals Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4487
Author(s):  
Masanori Nakata ◽  
Parmila Kumari ◽  
Rika Kita ◽  
Nanako Katsui ◽  
Yuriko Takeuchi ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Paraventricular Nucleus ◽  
Clock Gene ◽  
Clock Genes ◽  
Circadian Variation ◽  
Glucose And Lipid Metabolism ◽  
Clock Component

It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene Bmal1 in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The Sim1-Cre-mediated deletion of Bmal1 markedly reduced insulin secretion, resulting in impaired glucose tolerance. The pancreatic islets’ responses to glucose, sulfonylureas (SUs) and arginine vasopressin (AVP) were well maintained. To specify the PVN neuron subpopulation targeted by Bmal1, the expression of neuropeptides was examined. In these knockout (KO) mice, the mRNA expression of Avp in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed Avp expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains Avp expression in the PVN and release to the circulation, possibly providing islet b-cells with more AVP. This action helps enhance insulin release and, consequently, glucose tolerance. In contrast, the circadian variation of Avp expression is regulated by feeding, but not by PVN BMAL1.

Abstract 049: Role of Smooth Muscle BMAL1 in Time-of-day Vasoconstriction Variation and Blood Pressure Circadian Rhythm

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Zhongwen Xie ◽  
Wen Su ◽  
Shu Liu ◽  
Guogang Zhao ◽  
Karyn Esser ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Circadian Rhythm ◽  
Pulse Pressure ◽  
Clock Genes ◽  
Time Of Day ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Central Pacemaker

The blood pressure circadian rhythm was believed to be primarily controlled by the central pacemaker suprachiasmatic nucleus (SCN). This dogma was challenged by the discoveries that each of the clock genes present in the SCN are also expressed and function in peripheral tissues. But whether, and if so how, the peripheral clock genes are involved remains uncertain. The current study investigates the role of Bmal1, an obligatory core clock gene, plays in smooth muscle and blood pressure regulation by using a smooth muscle specific BMAL1 knockout mouse model (SM-Bmal1-KO). The results show: 1) Smooth muscle specific deletion of BMAL1 does not affect the clock genes in SCN but drastically suppresses the amplitude and the time-of day differences in vasoconstriction in response to various agonist stimulation and to perfusion pressure increase in isolated small mesenteric arteries and pressor responses in anesthetized mice; 2) The inhibition of agonist-induced vasoconstriction is associated with suppression of MLC 20 phosphorylation, ROCK2 mRNA and activity. Moreover, BMAL1 directly binds to ROCK2 promoter in a time-of-day dependent manner in mesenteric arteries and is required for ROCK2 promoter activity in cultured vascular smooth muscle cells; 3) Mice lacking smooth muscle BMAL1, but not those lacking cardiomyocyte BMAL1, exhibits alterations in blood pressure. SM-Bmal1-KO mice have moderately but significantly decreased blood pressure under 12:12 light/dark cycle, constant dark, and constant light conditions. The blood pressure circadian rhythm in SM-Bmal1-KO mice has diminished amplitude, forward shifted acrophase, but normal period length and normal locomotor activity; 4) interestingly, pulse pressure is markedly elevated and the pulse pressure circadian rhythm is abolished in the SM-Bmal1-KO mice. These data provide novel mechanistic insights into the daily control of vasoconstriction and blood pressure, which are fundamentally significant for the elucidation of pathogenesis of diseases involving blood pressure circadian rhythm disruption.

Role of intestinal microbiota in cardiovascular diseases

2020 ◽  
Vol 18 (1) ◽  
pp. 54-59
Author(s):  
R. A. FAYZULLINA ◽  
◽  
K. A. SAFINA ◽  
Keyword(s):  
Cardiovascular Diseases ◽  
Intestinal Microbiota

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

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