Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

Akashi, Makoto; Matsumura, Ritsuko; Matsuo, Takahiro; Kubo, Yuki; Komoda, Hiroshi; Node, Koichi

doi:10.1016/j.ebiom.2017.04.034

Cited by 19 publications

(13 citation statements)

References 35 publications

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“…28 per2 has been the focus of studies regarding cardiovascular diseases. 29 In this study, we demonstrated a circadian pattern of per2 protein expression and the LC3-II/I ratio in the mouse heart. Previous studies had found that there was a circadian rhythmicity of MI incidence, infarct size, and clinical outcomes in STEMI.…”

Section: Discussionmentioning

confidence: 49%

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

et al. 2020

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Accumulating evidence indicates that the onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MIs that occur in the early morning have a poor prognosis, but the mechanisms involved are still unknown. In this study, we showed that the expression level of Period 2 (per2) in the heart of mice is lower in the early morning than at noon and that increasing the expression of per2 in H9C2 cells and rat cardiomyocytes increases autophagy levels. Further studies indicated that overexpression of per2 after an MI improved cardiac function by increasing autophagy. In summary, this study has shown that the circadian clock protein, per2, may be a regulator of MI.

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Section: Discussionmentioning

confidence: 49%

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

et al. 2020

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“…CCGs are involved in various physiological activities, including cell proliferation, apoptosis, cell cycling, metabolism, endocrine signaling and immunity (4)(5)(6)(7)(8). As a result, abnormal expression of clock genes can lead to a variety of diseases, including endocrine disorders, cardiovascular diseases and tumors (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Xiong

Yang

et al. 2017

Int J Oncol

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Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types. However, the expression of PER2 in oral squamous cell carcinoma (OSCC), a common malignant tumor in humans, and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear. In the present study, we detected the mRNA and protein expression levels of PER2, PIK3CA, PTEN, P53, P14ARF and caspase‑8 in OSCC tissues and cancer-adjacent oral mucosa by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry. The results showed that the PER2, PTEN, P53, P14ARF and caspase‑8 mRNA and protein expression levels in OSCC were significantly reduced compared with those in cancer-adjacent tissues. Additionally, the PIK3CA protein expression level was significantly increased in OSCC tissues, whereas the mRNA level was not. Decreased expression of PER2 was signiﬁcantly associated with advanced clinical stage and the presence of lymphatic metastasis in OSCC patients. Patients with PER2‑negative expression had a significantly shorter survival time than those with PER2‑positive expression. PER2 expression was negatively correlated with PIK3CA and P53 levels, and positively correlated with PTEN, P14ARF and caspase‑8 levels. In summary, the results of this study suggest that loss of PER2 expression is closely associated with the genesis and development of OSCC and that PER2 may be an important prognostic biomarker in OSCC. PER2 may serve an antitumor role via the P53/P14ARF, PIK3CA/AKT and caspase‑8 pathways.

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“…A clinical study by Mergeani et al (2015) demonstrated that increased total and low density lipoprotein (LDL) cholesterol are significantly associated with a disrupted circadian rhythm of BP [ 34 ]. Interestingly, mice lacking functional LDL-receptor, an animal model of human familial hypercholesterolemia, exhibit abnormal circadian behavior [ 35 ]. Additionally, the introduction of a genetic mutation in the Per 2 gene resulted in mice with a significant enlargement of artery plaque area and increased levels of the inflammatory cytokine interleukin 6 (IL-6).…”

Section: The Circadian Timing System and Diurnal Variation Of Bp Imentioning

confidence: 99%

Altered Circadian Timing System-Mediated Non-Dipping Pattern of Blood Pressure and Associated Cardiovascular Disorders in Metabolic and Kidney Diseases

Rahman

Hasan

Nishiyama

et al. 2018

IJMS

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The morning surge in blood pressure (BP) coincides with increased cardiovascular (CV) events. This strongly suggests that an altered circadian rhythm of BP plays a crucial role in the development of CV disease (CVD). A disrupted circadian rhythm of BP, such as the non-dipping type of hypertension (i.e., absence of nocturnal BP decline), is frequently observed in metabolic disorders and chronic kidney disease (CKD). The circadian timing system, controlled by the central clock in the suprachiasmatic nucleus of the hypothalamus and/or by peripheral clocks in the heart, vasculature, and kidneys, modulates the 24 h oscillation of BP. However, little information is available regarding the molecular and cellular mechanisms of an altered circadian timing system-mediated disrupted dipping pattern of BP in metabolic disorders and CKD that can lead to the development of CV events. A more thorough understanding of this pathogenesis could provide novel therapeutic strategies for the management of CVD. This short review will address our and others’ recent findings on the molecular mechanisms that may affect the dipping pattern of BP in metabolic dysfunction and kidney disease and its association with CV disorders.

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Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

Cited by 19 publications

References 35 publications

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Altered Circadian Timing System-Mediated Non-Dipping Pattern of Blood Pressure and Associated Cardiovascular Disorders in Metabolic and Kidney Diseases

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