Roles of Nuclear Receptors in Vascular Calcification

Chinetti-Gbaguidi, Giulia; Neels, Jaap G.

doi:10.3390/ijms22126491

Cited by 3 publications

(4 citation statements)

References 159 publications

(186 reference statements)

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“…Low plasma concentrations of clotting factors II and VII have been associated with increased risk of cardiovascular mortality in elderly with signs of heart failure [13]. It is worth noting that vitamin K may also work via a nuclear receptor as a specific form of vitamin K, i.e., menaquinone 4 (MK4), may activate the steroid and xenobiotic receptor (SRX), the human analogue of the pregnane and xenobiotic receptor (PXR) in rodents [14]. Activated MGP is a potent inhibitor of vascular calcification, while osteocalcin is essential for bone mineralization [15,16].…”

Section: Sources and Kinetics Of Vitamin Kmentioning

confidence: 99%

“…Another mechanism by which vitamin K can affect vascular calcification is interaction with the SXR nuclear receptor (or its rodent homologue, the pregnane xenobiotic receptor (PXR)) [14]. SXR/PXR heterodimerizes with retinoid X receptor (RXR) The importance of vitamin K in carboxylation is underlined by the fact that its deficiency, by leading to an impaired carboxylation and reduced activity of VKDPs, can lead to health problems, such as bleeding disorders [47] and impaired cardiovascular health [48].…”

Section: Vitamin K Human Steroid and Xenobiotic Receptor (Sxr) And In...mentioning

confidence: 99%

“…Another mechanism by which vitamin K can affect vascular calcification is interaction with the SXR nuclear receptor (or its rodent homologue, the pregnane xenobiotic receptor (PXR)) [14]. SXR/PXR heterodimerizes with retinoid X receptor (RXR) after ligand binding, and MK4 is the only vitamin K homologue that binds to and activate SXR/PXR [55].…”

Section: Vitamin K Human Steroid and Xenobiotic Receptor (Sxr) And In...mentioning

confidence: 99%

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Vitamin K and Calcium Chelation in Vascular Health

Aaseth,

Alehagen,

Opstad

et al. 2023

Biomedicines

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The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.

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Section: Sources and Kinetics Of Vitamin Kmentioning

confidence: 99%

Section: Vitamin K Human Steroid and Xenobiotic Receptor (Sxr) And In...mentioning

confidence: 99%

“…Another mechanism by which vitamin K can affect vascular calcification is interaction with the SXR nuclear receptor (or its rodent homologue, the pregnane xenobiotic receptor (PXR)) [14]. SXR/PXR heterodimerizes with retinoid X receptor (RXR) after ligand binding, and MK4 is the only vitamin K homologue that binds to and activate SXR/PXR [55].…”

Section: Vitamin K Human Steroid and Xenobiotic Receptor (Sxr) And In...mentioning

confidence: 99%

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Vitamin K and Calcium Chelation in Vascular Health

Aaseth,

Alehagen,

Opstad

et al. 2023

Biomedicines

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“…For a long time, vascular calcification was considered the end stage of AS. Research results show that vascular wall calcification is not a static and random process, but an active and strictly regulated process ( 201 ). AGEs-induced VSMCs convert to osteogenic phenotype and overexpressing osteogenic markers (CBFα-1, ALP and osteocalcin) expression, resulting in to unbalance of bone metabolism and calcification of vascular wall ( 120 , 202 , 203 ).…”

Section: Calcification and Osteogenic Differentiationmentioning

confidence: 99%

Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis

Lin

Yin²,

Yang³

et al. 2022

Front. Endocrinol.

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Atherosclerosis (AS) is a chronic inflammatory disease and leading cause of cardiovascular diseases. The progression of AS is a multi-step process leading to high morbidity and mortality. Hyperglycemia, dyslipidemia, advanced glycation end products (AGEs), inflammation and insulin resistance which strictly involved in diabetes are closely related to the pathogenesis of AS. A growing number of studies have linked AGEs to AS. As one of the risk factors of cardiac metabolic diseases, dysfunction of VSMCs plays an important role in AS pathogenesis. AGEs are increased in diabetes, participate in the occurrence and progression of AS through multiple molecular mechanisms of vascular cell injury. As the main functional cells of vascular, vascular smooth muscle cells (VSMCs) play different roles in each stage of atherosclerotic lesions. The interaction between AGEs and receptor for AGEs (RAGE) accelerates AS by affecting the proliferation and migration of VSMCs. In addition, increasing researches have reported that AGEs promote osteogenic transformation and macrophage-like transformation of VSMCs, and affect the progression of AS through other aspects such as autophagy and cell cycle. In this review, we summarize the effect of AGEs on VSMCs in atherosclerotic plaque development and progression. We also discuss the AGEs that link AS and diabetes mellitus, including oxidative stress, inflammation, RAGE ligands, small noncoding RNAs.

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Roles of Nuclear Receptors in Esophageal Cancer

Deng

Liu

Chen

et al. 2023

CPB

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Background: Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression. Objectives: NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC. Method: This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments. Results: NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC. Conclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseasesConclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases

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Roles of Nuclear Receptors in Vascular Calcification

Cited by 3 publications

References 159 publications

Vitamin K and Calcium Chelation in Vascular Health

Vitamin K and Calcium Chelation in Vascular Health

Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis

Roles of Nuclear Receptors in Esophageal Cancer

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