Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis

Chen, Chuanzhen; Li, Yaodong; Lu, Hailin; Li, Kai; Jiang, Wenhong; Zhang, Zhanman; Qin, Xiao

doi:10.1177/15353702221095456

Cited by 9 publications

(8 citation statements)

References 46 publications

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“…found that rosmarinic acid (RA), a common phenolic compound that possesses antioxidation, anti-inflammatory, and antimicrobial effects, improves VC by regulating the Nrf2 pathway and significantly reduced the levels of ALP, MDA, Ca, and P but increases SOD levels [ 40 ]. Curcumin (CUR) was a natural polyphenolic antioxidant compound that increased miR-92b-3p expression and decreased KLF4 expression in the aorta thereby attenuating vitamin D3-induced VC [ 41 ]. Furthermore, Huang et al.…”

Section: Discussionmentioning

confidence: 99%

Dietary lycopene is negatively associated with abdominal aortic calcification in US adults: a cross-sectional study

Liu

et al. 2023

Annals of Medicine

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Background Vascular calcification (VC) is one of the complications of chronic kidney disease (CKD) patients. Previous studies have confirmed that oxidative stress (OS) plays an important role in developing VC and that antioxidants have anti-VC effects. Objectives Our study aimed to determine the relationship between the intake of antioxidants from dietary sources and the prevalence of VC, especially in the CKD population. Methods This cross-sectional study analyzed population-based data from the National Health and Nutrition Examination Survey (NHANES; 2013–2014). Participants were noninstitutionalized adults >40 years of age. Diet-derived antioxidants were obtained from the first 24-h dietary recall interviews. The abdominal aortic calcification (AAC) score was measured by a DXA scan. We divided the AAC scores into three groups: no calcification (AAC =0), mild to moderate calcification (0< AAC ≤6), and severe calcification (AAC >6). Results A total of 2897 participants were included in the main analysis. Our results showed that vitamin B6, α-tocopherol, and lycopene were associated with severe AAC in unadjusted models (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.72–0.91, p = 0.001; OR: 0.97, 95% CI: 0.95–0.99, p = 0.008; OR: 0.98, 95% CI: 0.96–0.99, p = 0.01, respectively). However, only dietary lycopene was associated with severe AAC after adjusting covariates based on clinical and statistical significance. Per 1 mg higher intake of diet-derived lycopene per day, the odds of having severe AAC were 2% lower in the fully adjusted model (OR: 0.98, 95% CI: 0.95–0.999, p = 0.04). Moreover, in subgroup analysis, diet-derived antioxidant was not associated with AAC in patients with CKD. Conclusion: Our findings indicate that a higher intake of diet-derived lycopene was independently associated with lower odds of having severe AAC in humans. Therefore, a high intake of diet-derived lycopene may help prevent severe AAC.

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Section: Discussionmentioning

confidence: 99%

Dietary lycopene is negatively associated with abdominal aortic calcification in US adults: a cross-sectional study

Liu

et al. 2023

Annals of Medicine

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“…Nevertheless, there have been few reports of miR-92b-3p's role in osteoblast differentiation. Intriguingly, Chen et al proposed that miR-92b-3p impeded vascular calcification through decreasing KLF4 and Runx2 expression in vascular smooth muscle cells [40]. Gain-and loss-of-function experiments utilizing miR-92b-3p mimic or inhibitor, respectively, proved that miR-92b-3p impaired osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from Microvascular Endothelial Cells under Mechanical Unloading Inhibit Osteogenic Differentiation via miR-92b-3p/ELK4 Axis

Zhang

et al. 2022

JPM

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Mechanical unloading-related bone loss adversely harms astronauts’ health. Nevertheless, the specific molecular basis underlying the phenomenon has not been completely elucidated. Although the bone microvasculature contributes significantly to bone homeostasis, the pathophysiological role of microvascular endothelial cells (MVECs) in bone loss induced by mechanical unloading is not apparent. Here, we discovered that MC3T3-E1 cells could take up exosomes produced by MVECs under clinorotation-unloading conditions (Clino Exos), which then prevented MC3T3-E1 cells from differentiating into mature osteoblasts. Moreover, miR-92b-3p was found to be highly expressed in both unloaded MVECs and derived exosomes. Further experiments demonstrated that miR-92b-3p was transferred into MC3T3-E1 cells by exosomes, resulting in the suppression of osteogenic differentiation, and that encapsulating miR-92b-3p inhibitor into the Clino Exos blocked their inhibitory effects. Furthermore, miR-92b-3p targeted ELK4 and the expression of ELK4 was lessened when cocultured with Clino Exos. The inhibitor-92b-3p-promoted osteoblast differentiation was partially reduced by siRNA-ELK4. Exosomal miR-92b-3p secreted from MVECs under mechanical unloading has been shown for the first time to partially attenuate the function of osteoblasts through downregulation of ELK4, suggesting a potential strategy to protect against the mechanical unloading-induced bone loss and disuse osteoporosis.

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“…For example, curcumin (CUR) and exosomes secreted by VSMCs after CUR intervention attenuated VC. In vitro, CUR intervention resulted in high miR-92b-3p expression in both VSMCs and exosomes and delivery of miR-92b-3p to adjacent cells, significantly reducing expression of the transcription factor KLF4 and osteogenic factor RUNX2 in VSMCs; in addition, in a rat calcification model, CUR attenuated vitamin D3-induced VC by increasing miR-92b-3p expression and decreasing KLF4 expression in the aorta (94). Melatonin induced VSMCs to produce exosomes carrying miR-204 and miR-211, which inhibited BMP-2 expression in adjacent cells in a paracrine manner and attenuated VC and senescence (95).…”

Section: Exosomes and Vascular Calcificationmentioning

confidence: 94%

Emerging role of exosomes in vascular diseases

Ren

Zhang

2023

Front. Cardiovasc. Med.

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Exosomes are biological small spherical lipid bilayer vesicles secreted by most cells in the body. Their contents include nucleic acids, proteins, and lipids. Exosomes can transfer material molecules between cells and consequently have a variety of biological functions, participating in disease development while exhibiting potential value as biomarkers and therapeutics. Growing evidence suggests that exosomes are vital mediators of vascular remodeling. Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), inflammatory cells, and adventitial fibroblasts (AFs) can communicate through exosomes; such communication is associated with inflammatory responses, cell migration and proliferation, and cell metabolism, leading to changes in vascular function and structure. Essential hypertension (EH), atherosclerosis (AS), and pulmonary arterial hypertension (PAH) are the most common vascular diseases and are associated with significant vascular remodeling. This paper reviews the latest research progress on the involvement of exosomes in vascular remodeling through intercellular information exchange and provides new ideas for understanding related diseases.

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Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis

Cited by 9 publications

References 46 publications

Dietary lycopene is negatively associated with abdominal aortic calcification in US adults: a cross-sectional study

Dietary lycopene is negatively associated with abdominal aortic calcification in US adults: a cross-sectional study

Exosomes from Microvascular Endothelial Cells under Mechanical Unloading Inhibit Osteogenic Differentiation via miR-92b-3p/ELK4 Axis

Emerging role of exosomes in vascular diseases

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