Loss of CLOCK under high glucose upregulates ROCK1-mediated endothelial to mesenchymal transition and aggravates plaque vulnerability

Tang, Hanfei; Zhu, Meiying; Zhao, Gaofeng; Fu, Weiguo; Shi, Zhenyu; Ding, Yong; Tang, X.; Guo, Daqiao

doi:10.1016/j.atherosclerosis.2018.05.046

Cited by 22 publications

(15 citation statements)

References 24 publications

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“…The possibility that apolipoprotein A1 (ApoA1) may abrogate the activation of the EndMT process induced by TGF-␤ was examined in vitro employing human coronary artery endothelial cells, and it was shown that ApoA1 reduced the expression levels of the key transcriptional activators mediating EndMT, Snail and Slug, and caused a potent inhibition of EndMT in these cells (95). Another mechanistic investigation examined the role of the CLOCK gene in the development of EndMT in HUVECs cultured in high glucose and in carotid artery endothelium of patients with carotid artery stenosis (302). The results uncovered a unique mechanism by which CLOCK suppresses EndMT reducing atherosclerotic development, and a strong positive relationship between loss of CLOCK expression, development of EndMT, and atherosclerotic plaque vulnerability was demonstrated.…”

Section: Vascular Diseasesmentioning

confidence: 99%

Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Piera-Velázquez

Jimenez

2019

Physiological Reviews

425

322

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Numerous studies have demonstrated that endothelial cells are capable of undergoing endothelial to mesenchymal transition (EndMT), a newly recognized type of cellular transdifferentiation. EndMT is a complex biological process in which endothelial cells adopt a mesenchymal phenotype displaying typical mesenchymal cell morphology and functions, including the acquisition of cellular motility and contractile properties. Endothelial cells undergoing EndMT lose the expression of endothelial cell-specific proteins such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and initiate the expression of mesenchymal cell-specific genes and the production of their encoded proteins including α-smooth muscle actin, extra domain A fibronectin, N-cadherin, vimentin, fibroblast specific protein-1, also known as S100A4 protein, and fibrillar type I and type III collagens. Transforming growth factor-β1 is considered the main EndMT inducer. However, EndMT involves numerous molecular and signaling pathways that are triggered and modulated by multiple and often redundant mechanisms depending on the specific cellular context and on the physiological or pathological status of the cells. EndMT participates in highly important embryonic development processes, as well as in the pathogenesis of numerous genetically determined and acquired human diseases including malignant, vascular, inflammatory, and fibrotic disorders. Despite intensive investigation, many aspects of EndMT remain to be elucidated. The identification of molecules and regulatory pathways involved in EndMT and the discovery of specific EndMT inhibitors should provide novel therapeutic approaches for various human disorders mediated by EndMT.

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Section: Vascular Diseasesmentioning

confidence: 99%

Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Piera-Velázquez

Jimenez

2019

Physiological Reviews

425

322

View full text Add to dashboard Cite

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“…The circadian gene CLOCK has protective effects against atherosclerosis. CLOCK over-expression attenuates the endothelial damage induced by high glucose [147]. Moreover, knockout of the CLOCK gene in mice with carotid artery ligation increases neointima formation and neovascularization [148].…”

Section: Disrupted Circadian Rhythmmentioning

confidence: 99%

“…Moreover, knockout of the CLOCK gene in mice with carotid artery ligation increases neointima formation and neovascularization [148]. In a human carotid plaque sample, the expression level of CLOCK was also negatively correlated with plaque vulnerability, as well as the presence of atherosclerotic risk factors [147,148]. Another circadian gene, brain and muscle Arnt-like protein-1 (BMAL1), plays an essential role in circadian rhythms, the loss of which can cause abnormality including aging, aberrant blood glucose level, shortened longevity, and aggravated atherosclerosis [149].…”

Section: Disrupted Circadian Rhythmmentioning

confidence: 99%

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

Zhang

et al. 2021

Molecules

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Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation.

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“…Indeed, studies have indicated that the functional circadian clock exists within the vasculature ( 47 ). A growing number of studies ( 48-55 ) have identified that circadian clocks regulate the functions of endothelial cells, VSMCs and macrophages, suggesting the possibility of circadian clocks to influence the progression of atherosclerosis (as presented in Fig. 2 ).…”

Section: Circadian Rhythm and Vascular Cellsmentioning

confidence: 99%

“…Furthermore, endothelial cell activation leads to expression of adhesion molecules, loss of barrier function, migration of leukocytes into the vascular wall and improvement in inﬂammatory responses ( 46 ). Tang et al ( 48 ) indicated that loss of protective endothelial Clock expression contributes to the progression of atherosclerosis and aggravates plaque vulnerability. It appears that the circadian clock is able to regulate the release of nitric oxide (NO) and disruption of the clock leads to endothelial dysfunction ( 56 ).…”

Section: Circadian Rhythm and Vascular Cellsmentioning

confidence: 99%

Circadian rhythm and atherosclerosis (Review)

Zhang

Wang

et al. 2020

Exp Ther Med

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Atherosclerosis is the leading cause of morbidity and mortality worldwide. The underlying pathogenesis involves multiple metabolic disorders, endothelial dysfunction and a maladaptive immune response, and leads to chronic arterial wall inflammation. Numerous normal physiological activities exhibit daily rhythmicity, including energy metabolism, vascular function and inflammatory immunoreactions, and disrupted or misaligned circadian rhythms may promote the progression of atherosclerosis. However, the association between the circadian rhythm and atherosclerosis remains to be fully elucidated. In the present review, the effects of the circadian rhythm on atherosclerosis progression are discussed.

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Loss of CLOCK under high glucose upregulates ROCK1-mediated endothelial to mesenchymal transition and aggravates plaque vulnerability

Cited by 22 publications

References 24 publications

Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

Circadian rhythm and atherosclerosis (Review)

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