Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

Man, Andy W C; Li, Huige; Xia, Ning

doi:10.3390/ijms22020676

Cited by 41 publications

(36 citation statements)

References 184 publications

(138 reference statements)

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“…Circadian rhythms can influence the pathology of arteriosclerosis and thrombosis [23]. It is known that many thromboembolic events occur during the early hours of the day because of a high proclivity for platelet aggregation and vasoconstriction during the early morning hours.…”

Section: Discussionmentioning

confidence: 99%

A Study on Chronofatality Trends of COVID-19 Deaths at a Tertiary Care Hospital

et al. 2021

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The aim of the study is to find out any association between time of death in coronavirus disease (COVID-19) patients and variables like age, sex, and existence of comorbidities including type II diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, etc. An attempt was also made to elucidate the reasons for relationship between time of death and other aforementioned variables. Mortality data of 1,553 COVID-19 cases from a tertiary care hospital between March 2020 to September 2021 were analyzed. Maximum deaths occurred between 18:01 hours to 06:00 hours of the 24-hour cycle. There is a significant statistical association between time of death and age, time of death and sex, time of death and having a comorbidity of diabetes mellitus in the study sample. The study confirms that the chronofatality of COVID-19 deaths has a nocturnal predilection. The circadian rhythms of glucocorticoids, respiratory physiology of sleep, and circadian hemodynamic variations may have a role in prognosis and fatality of COVID-19.

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Section: Discussionmentioning

confidence: 99%

A Study on Chronofatality Trends of COVID-19 Deaths at a Tertiary Care Hospital

et al. 2021

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“…In the vasculature, a functional circadian clock has been demonstrated in the different types of cells in the vascular wall, and different components of the molecular circadian clock have been demonstrated in endothelial cells, in the VSMC of lamina media and in cultured fibroblasts from the adventitia of the arteries [ 20 , 63 , 64 , 65 , 66 ]. With the generation of genetically altered mice models, some important features of the intrinsic vascular circadian clock in cardiovascular pathology have been uncovered [ 20 , 67 ]. As such, in several animal studies, circadian rhythm disruption was achieved either by genetically modifying the molecular circadian clock in the individual cells in the cardiovascular system or by the global deletion of core molecular circadian clock genes.…”

Section: The Internal Vascular Circadian Clock and Its Role In Vascular Pathologymentioning

confidence: 99%

“…Both Bmal1 −/− and Clock-mutant mice exhibited impaired vasorelaxation in response to acetylcholine [ 76 ]. Excellent review articles have been published recently that have highlighted the importance of the circadian clock in the cardiovascular system [ 20 , 67 ].…”

Section: The Internal Vascular Circadian Clock and Its Role In Vascular Pathologymentioning

confidence: 99%

The Vascular Circadian Clock in Chronic Kidney Disease

Egstrand

Mace

Ølgaard

et al. 2021

Cells

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Chronic kidney disease is associated with extremely high cardiovascular mortality. The circadian rhythms (CR) have an impact on vascular function. The disruption of CR causes serious health problems and contributes to the development of cardiovascular diseases. Uremia may affect the master pacemaker of CR in the hypothalamus. A molecular circadian clock is also expressed in peripheral tissues, including the vasculature, where it regulates the different aspects of both vascular physiology and pathophysiology. Here, we address the impact of CKD on the intrinsic circadian clock in the vasculature. The expression of the core circadian clock genes in the aorta is disrupted in CKD. We propose a novel concept of the disruption of the circadian clock system in the vasculature of importance for the pathology of the uremic vasculopathy.

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“…How these cardiovascular effects are manifested is not presently well understood. Inasmuch as circadian rhythms of neuroendocrine events, including autonomic balance, within the cardiovascular system play major roles in cardiovascular health including control of blood pressure, vascular endothelial function, cardiomyocyte biology, and daily cardiac rhythmicity [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ], it was postulated that such neuroendocrine modulation by bromocriptine-QR may contribute to its observed beneficial effects on adverse cardiovascular outcomes. Since the impact of bromocriptine-QR on cardiovascular disease (CVD) was so rapid and increases or decreases in vascular oxidative and nitrosative stress can rapidly and significantly worsen or improve cardiovascular health, respectively, in individuals with dysmetabolism [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] (insulin resistance, obesity, T2D, or metabolic syndrome (a composite of obesity, dyslipidemia, hypertension, and associated low grade systemic inflammation)), this study investigated the potential impact of circadian-timed bromocriptine administration to improve vascular oxidative/nitrosative pathology in hypertensive SHR rats induced to generate metabolic syndrome by maintenance on a high fat diet.…”

Section: Introductionmentioning

confidence: 99%

Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet

Ezrokhi

Zhang

Luo

et al. 2021

IJMS

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The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug’s cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease. Therefore, this study investigated the impact of bromocriptine treatment upon biomarkers of vascular oxidative/nitrosative stress (including the pro-oxidative/nitrosative stress enzymes of NADPH oxidase 4, inducible nitric oxide (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), the pro-inflammatory/pro-oxidative marker GTP cyclohydrolase 1 (GTPCH 1), and the pro-vascular health enzyme, soluble guanylate cyclase (sGC) as well as the plasma level of thiobarbituric acid reactive substances (TBARS), a circulating marker of systemic oxidative stress), in hypertensive SHR rats held on a high fat diet to induce metabolic syndrome. Inasmuch as the central nervous system (CNS) dopaminergic activities both regulate and are regulated by CNS circadian pacemaker circuitry, this study also investigated the time-of-day-dependent effects of bromocriptine treatment (10 mg/kg/day at either 13 or 19 h after the onset of light (at the natural waking time or late during the activity period, respectively) among animals held on 14 h daily photoperiods for 16 days upon such vascular biomarkers of vascular redox state, several metabolic syndrome parameters, and mediobasal hypothalamic (MBH) mRNA expression levels of neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) which regulate the peripheral fuel metabolism and of mRNA expression of other MBH glial and neuronal cell genes that support such metabolism regulating neurons in this model system. Such bromocriptine treatment at ZT 13 improved (reduced) biomarkers of vascular oxidative/nitrosative stress including plasma TBARS level, aortic NADPH oxidase 4, iNOS and GTPCH 1 levels, and improved other markers of coupled eNOS function, including increased sGC protein level, relative to controls. However, bromocriptine treatment at ZT 19 produced no improvement in either coupled eNOS function or sGC protein level. Moreover, such ZT 13 bromocriptine treatment reduced several metabolic syndrome parameters including fasting insulin and leptin levels, as well as elevated systolic and diastolic blood pressure, insulin resistance, body fat store levels and liver fat content, however, such effects of ZT 19 bromocriptine treatment were largely absent versus control. Finally, ZT 13 bromocriptine treatment reduced MBH NPY and AgRP mRNA levels and mRNA levels of several MBH glial cell/neuronal genes that code for neuronal support/plasticity proteins (suggesting a shift in neuronal structure/function to a new metabolic control state) while ZT 19 treatment reduced only AgRP, not NPY, and was with very little effect on such MBH glial cell genes expression. These findings indicate that circadian-timed bromocriptine administration at the natural circadian peak of CNS dopaminergic activity (that is diminished in insulin resistant states), but not outside this daily time window when such CNS dopaminergic activity is naturally low, produces widespread improvements in biomarkers of vascular oxidative stress that are associated with the amelioration of metabolic syndrome and reductions in MBH neuropeptides and gene expressions known to facilitate metabolic syndrome. These results of such circadian-timed bromocriptine treatment upon vascular pathology provide potential mechanisms for the observed marked reductions in adverse cardiovascular events with circadian-timed bromocriptine-QR therapy (similarly timed to the onset of daily waking as in this study) of type 2 diabetes subjects and warrant further investigations into related mechanisms and the potential application of such intervention to prediabetes and metabolic syndrome patients as well.

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Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

Cited by 41 publications

References 184 publications

A Study on Chronofatality Trends of COVID-19 Deaths at a Tertiary Care Hospital

A Study on Chronofatality Trends of COVID-19 Deaths at a Tertiary Care Hospital

The Vascular Circadian Clock in Chronic Kidney Disease

Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet

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