Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages

Ou, Han-Xiao; Huang, Qin; Liu, Chuhao; Xiao, Ji; Lv, Yun-Cheng; Li, Xuan; Lei, Lili; Zhang, Mo

doi:10.1253/circj.cj-19-0430

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…Although without statistical significance, MK probably also contributed to the migration of vascular smooth muscle cells in atherosclerosis ( 90 ). Moreover, a recent investigation demonstrated that MK encouraged lipid accumulation in macrophages ( 134 ), critical for foam cell generation which are indispensable for atherosclerotic plaque formation ( 133 ). In this regard, MK induced the downregulation of adenosine triphosphate-binding membrane cassette transport protein A1, resulting in decreased cholesterol efflux ( 134 ).…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

“…Moreover, a recent investigation demonstrated that MK encouraged lipid accumulation in macrophages ( 134 ), critical for foam cell generation which are indispensable for atherosclerotic plaque formation ( 133 ). In this regard, MK induced the downregulation of adenosine triphosphate-binding membrane cassette transport protein A1, resulting in decreased cholesterol efflux ( 134 ). Also, adenosine monophosphate activated protein-mammalian target of rapamycin signaling was found to be involved in MK-mediated cholesterol metabolism regulation in macrophages ( 134 ).…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

“…In this regard, MK induced the downregulation of adenosine triphosphate-binding membrane cassette transport protein A1, resulting in decreased cholesterol efflux ( 134 ). Also, adenosine monophosphate activated protein-mammalian target of rapamycin signaling was found to be involved in MK-mediated cholesterol metabolism regulation in macrophages ( 134 ). Thus, MK drove atherosclerotic plaque formation through its pro-inflammatory, pro-angiogenic and anti-apoptotic effects combined with its inhibition of macrophage cholesterol efflux.…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

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Midkine—A novel player in cardiovascular diseases

Majaj

Weckbach

2022

Front. Cardiovasc. Med.

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Midkine (MK) is a 13-kDa heparin-binding cytokine and growth factor with anti-apoptotic, pro-angiogenic, pro-inflammatory and anti-infective functions, that enable it to partake in a series of physiological and pathophysiological processes. In the past, research revolving around MK has concentrated on its roles in reproduction and development, tissue protection and repair as well as inflammatory and malignant processes. In the recent few years, MK's implication in a wide scope of cardiovascular diseases has been rigorously investigated. Nonetheless, there is still no broadly accepted consensus on whether MK exerts generally detrimental or favorable effects in cardiovascular diseases. The truth probably resides somewhere in-between and depends on the underlying physiological or pathophysiological condition. It is therefore crucial to thoroughly examine and appraise MK's participation in cardiovascular diseases. In this review, we introduce the MK gene and protein, its multiple receptors and signaling pathways along with its expression in the vascular system and its most substantial functions in cardiovascular biology. Further, we recapitulate the current evidence of MK's expression in cardiovascular diseases, addressing the various sources and modes of MK expression. Moreover, we summarize the most significant implications of MK in cardiovascular diseases with particular emphasis on MK's advantageous and injurious functions, highlighting its ample diagnostic and therapeutic potential. Also, we focus on conflicting roles of MK in a number of cardiovascular diseases and try to provide some clarity and guidance to MK's multifaceted roles. In summary, we aim to pave the way for MK-based diagnostics and therapies that could present promising tools in the diagnosis and treatment of cardiovascular diseases.

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Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Midkine—A novel player in cardiovascular diseases

Majaj

Weckbach

2022

Front. Cardiovasc. Med.

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“…To investigate the potential molecular mechanisms, we detected the expression of ABCA1, ABCG1 and LXRα. ABCA1 belongs to the ATP‐binding cassette family and is a major controller of cholesterol transport in macrophages (Ou et al., 2020). ABCG1 is upregulated by LXR and is also an ABC transporter translocating cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Danthron attenuates experimental atherosclerosis by targeting foam cell formation

Shi

Zhang

Lin

et al. 2021

Experimental Physiology

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New Findings What is the central question of this study?Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells? What are the main findings and their importance?Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE−/− mice. Danthron inhibited foam cell formation in oxidized low‐density lipoprotein‐induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP‐activated protein kinase–sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis. Abstract Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro. This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE−/− mice were fed a high‐fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low‐density lipoprotein (ox‐LDL, 50 μg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP‐activated protein kinase (AMPK) inhibitor compound C was added to ox‐LDL‐stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP‐binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK–sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox‐LDL‐induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK–SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro. Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK–SIRT1 signalling pathway.

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“…Mutations of the ATP binding cassette transporter A1 (ABCA1), a transmembrane protein involved in the intracellular cholesterol efflux to lipid-poor apolipoprotein A-I, leads to premature atherosclerosis. Ou et al [40] demonstrated that it downregulates ABCA1 expression by inhibiting the phosphorylation of AMP-activated protein kinase. This effect, also evidenced by other clinical studies, raises the hypothesis that blockade of cholesterol efflux via ABCA may lead to the arrest of the atherosclerotic process, being a future research direction in the pharmacological field of dyslipidemia.…”

Section: Midkine-a Biomarker For All Stages Of Atherosclerosismentioning

confidence: 99%

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

Adam¹,

Șalaru

Prisacariu

et al. 2022

IJMS

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The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions.

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Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages

Cited by 8 publications

References 33 publications

Midkine—A novel player in cardiovascular diseases

Midkine—A novel player in cardiovascular diseases

Danthron attenuates experimental atherosclerosis by targeting foam cell formation

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

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