Vitamin D deficiency induces pro-inflammatory phenotype of epicardial adipose tissue accelerating neointimal hyperplasia following coronary intervention

2018 ◽  
Vol 275 ◽  
pp. e48 ◽  
Author(s):  
D. Agrawal ◽  
V. Swier ◽  
P. Gunasekar ◽  
J. Fleegel ◽  
M. Radwan
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Epicardial Adipose Tissue ◽  
Neointimal Hyperplasia ◽  
Coronary Intervention ◽  
Inflammatory Phenotype

scholarly journals Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine

2012 ◽  
Vol 93 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Gaurav K. Gupta ◽  
Tanupriya Agrawal ◽  
Michael G. DelCore ◽  
Syed M. Mohiuddin ◽  
Devendra K. Agrawal
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Cardiac Hypertrophy ◽  
Vitamin D Deficiency ◽  
Epicardial Adipose Tissue

scholarly journals Vitamin D and Macrophage Polarization in Epicardial Adipose Tissue of Atherosclerotic Swine

2018 ◽  
Author(s):  
Palanikumar Gunasekar ◽  
Vicki J. Swier ◽  
Jonathan P. Fleegel ◽  
Chandra S. Boosani ◽  
Mohamed M. Radwan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Macrophage Polarization ◽  
Coronary Intervention ◽  
Vitamin D Supplementation ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Cellular Mechanisms ◽  
Significant Difference

AbstractVitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exacerbates inflammation by increasing pro-inflammatory M1 macrophages, while vitamin D-supplementation attenuates the inflammatory cytokines and promotes M2 macrophages in EAT. This study demonstrates the significance of vitamin D mediated inhibition of macrophage mediated inflammation in the EAT during coronary intervention in addition to its immunomodulatory role. However, additional studies are required to identify the cellular mechanisms that transduce signals between macrophages and smooth muscle cells during restenosis in the presence and absence of vitamin D.Author Contribution StatementDKA conceived and designed the experiments; PG, JPF, MMR performed the experiments; PG, JPF, VJS analyzed and interpreted the results; PG prepared the figures and wrote the initial draft of the manuscript; CSB, DKA revised and edited the revised manuscript.

scholarly journals Vitamin D signalling in adipose tissue

2012 ◽  
Vol 108 (11) ◽  
pp. 1915-1923 ◽  
Author(s):  
Cherlyn Ding ◽  
Dan Gao ◽  
John Wilding ◽  
Paul Trayhurn ◽  
Chen Bing
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
The Metabolic Syndrome ◽  
Prevalence Of Obesity ◽  
Adipose Tissue Development ◽  
And Function

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

scholarly journals Vitamin D Improves Nitric Oxide-Dependent Vasodilation in Adipose Tissue Arterioles from Bariatric Surgery Patients

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2521 ◽  
Author(s):  
Abeer M. Mahmoud ◽  
Mary Szczurek ◽  
Chandra Hassan ◽  
Mario Masrur ◽  
Antonio Gangemi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vitamin D ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Morbidly Obese ◽  
No Production ◽  
Obese Adults ◽  
Time Of Surgery ◽  
Post Surgery

There is a high prevalence of vitamin-D deficiency in obese individuals that could be attributed to vitamin-D sequestration in the adipose tissue. Associations between vitamin-D deficiency and unfavorable cardiometabolic outcomes were reported. However, the pathophysiological mechanisms behind these associations are yet to be established. In our previous studies, we demonstrated microvascular dysfunction in obese adults that was associated with reduced nitric oxide (NO) production. Herein, we examined the role of vitamin D in mitigating microvascular function in morbidly obese adults before and after weight loss surgery. We obtained subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies from bariatric patients at the time of surgery (n = 15) and gluteal SAT samples three months post-surgery (n = 8). Flow-induced dilation (FID) and acetylcholine-induced dilation (AChID) and NO production were measured in the AT-isolated arterioles ± NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME), hydrogen peroxide (H2O2) inhibitor, polyethylene glycol-modified catalase (PEG-CAT), or 1,25-dihydroxyvitamin D. Vitamin D improved FID, AChID, and NO production in AT-isolated arterioles at time of surgery; these effects were abolished by L-NAME but not by PEG-CAT. Vitamin-D-mediated improvements were of a higher magnitude in VAT compared to SAT arterioles. After surgery, significant improvements in FID, AChID, NO production, and NO sensitivity were observed. Vitamin-D-induced changes were of a lower magnitude compared to those from the time of surgery. In conclusion, vitamin D improved NO-dependent arteriolar vasodilation in obese adults; this effect was more significant before surgery-induced weight loss.

scholarly journals Vitamin D–vitamin D receptor system down-regulates expression of uncoupling proteins in brown adipocyte through interaction with Hairless protein

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Pei-qi Wang ◽  
Dao-xiang Pan ◽  
Chun-qiu Hu ◽  
Yu-lin Zhu ◽  
Xiao-jing Liu
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Brown Adipocyte ◽  
Dependent Manner ◽  
Cell Nuclei ◽  
Down Regulation ◽  
Brown Adipocytes ◽  
Brown Adipose

Abstract Our previous study showed that feeding mice with vitamin D deficiency diet markedly alleviated high-fat-diet-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency up-regulated the expression of uncoupling protein 3 (Ucp3) in white adipose tissue (WAT) and brown adipose tissue (BAT). The present study aimed to further investigate the effects of vitamin D and vitamin D receptor (Vdr) on Ucp1–3 (Ucps) expression in brown adipocyte and the mechanism involved in it. Rat primary brown adipocytes were separated and purified. The effects of the 1,25(OH)2D3 (1,25-dihydroxyvitamin D3; the hormonal form of vitamin D) and Vdr system on Ucps expression in brown adipocytes were investigated in basal condition and activated condition by isoproterenol (ISO) and triiodothyronine (T3). Ucps expression levels were significantly down-regulated by 1,25(OH)2D3 in the activated brown adipocyte. Vdr silencing reversed the down-regulation of Ucps by 1,25(OH)2D3, whereas Vdr overexpression strengthened the down-regulation effects. Hairless protein did express in brown adipocyte and was localized in cell nuclei. 1,25(OH)2D3 increased Hairless protein expression in the cell nuclei. Hairless (Hr) silencing notably elevated Ucps expression in activated condition induced by ISO and T3. Moreover, immunoprecipitation results revealed that Vdr could interact with Hairless, which might contribute to decreasing expression of Vdr target gene Ucps. These data suggest that vitamin D suppresses expression of Ucps in brown adipocyte in a Vdr-dependent manner and the corepressor Hairless protein probably plays a role in the down-regulation.

scholarly journals Vitamin D Deficiency Induces Macrophage Pro-Inflammatory Phenotype via ER Stress-Mediated Activation of Renin-Angiotensin System

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A304-A305
Author(s):  
Kevin Thomas Bauerle ◽  
Jisu Oh ◽  
Amy Elizabeth Riek ◽  
Adriana Dusso ◽  
Anabel L Castro-Grattoni ◽  
...  
Keyword(s):  
Vitamin D ◽  
Er Stress ◽  
Vitamin D Deficiency ◽  
Cytokine Production ◽  
Cytokine Release ◽  
Ras Gene ◽  
Macrophage Function ◽  
Renin Angiotensin ◽  
Vitamin D Levels ◽  
Inflammatory Phenotype

Abstract Chronic inflammation and local activation of the renin-angiotensin-aldosterone system (RAAS) play a pivotal role in the pathogenesis and progression of diabetic complications. In patients with type 2 diabetes (T2DM), the prevalence of vitamin D deficiency is almost twice that of non-diabetics, and vitamin d deficiency nearly doubles the risk of developing hypertension and cardiovascular complications compared to diabetics with normal vitamin D levels. Interestingly, mice lacking the vitamin D receptor (VDR) in macrophages (KODMAC) develop renin-dependent hypertension, insulin resistance, and inflammation via up-regulation of macrophage ER stress. Macrophages also express all major components of the RAAS system. However, little is known about the regulation of macrophage-generated renin and its role in modulating the sequelae of VDR signaling in macrophage function and cytokine production. This study found that KODMAC macrophages and vitamin D-deficient macrophages have increased expression and secretion of renin, angiotensin II, ACE, and AT1 receptor and that adhesion, migration, and cytokine release were also increased. Inhibition of ER stress in KODMAC macrophages and vitamin D-deficient macrophages with 4-Phenylbutyric acid (PBA) reduced RAS gene expression and macrophage pro-inflammatory phenotype. Renin 1c gene deletion decreased macrophage adhesion, migration, and cytokine release compared to macrophages with disrupted VDR signaling. Notably, disruption of VDR signaling induced peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in macrophages, and upregulation of renin expression in response to vitamin D deficiency was blunted in PCG1α-deficient macrophages. In conclusion, our findings delineate a mechanism by which impaired VDR signaling induces ER stress to drive PGC1α-dependent expression of renin and RAAS hyperactivation, thereby altering macrophage function and cytokine production. These data implicate RAAS as an essential mediator of VDR-mediated macrophage function and support ongoing investigations of VDR and RAAS modulation as therapeutic approaches in the management of T2DM and its complications.

scholarly journals The Value of Epicardial Adipose Tissue for the Patients Treated with Percutaneous Coronary Intervention: A Systemic Review and Meta-analysis

2020 ◽  
Author(s):  
Tan Xu ◽  
Ming Xu
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Adipose Tissue ◽  
Infarct Size ◽  
Epicardial Adipose Tissue ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Systemic Review ◽  
Standard Mean Difference ◽  
Percutaneous Coronary ◽  
The Relationship

Abstract BackgroundAccumulating evidences suggest that the prognostic value of epicardial adipose tissue (EAT) on no-reflow, in-stent restenosis (ISR), infarct size, and main adverse cardiovascular events (MACE) for the patients treated with percutaneous coronary intervention (PCI). The relationship between EAT and outcomes of patients underwent PCI is still partly elusive. MethodsTo elucidate the relationship in detail, we searched PubMed, web of science, and the Cochrane Library for studies evaluating the association of EAT and patients treated with PCI. Thirteen studies enrolling 3683 patients were eventually include in our systemic review and meta-analysis. ResultsThe EAT measured by thickness or volume was significantly higher in the ISR group compared to those in the non-ISR group (The standard mean difference -0.34, 95% CI, -0.49, -0.18, p <0.0001; I2 =36%). The incidence of no-reflow was significantly higher in thicker EAT group compared to thin EAT group (pooled relative ratio 1.52, 95%CI 1.29-1,80, p <0.0001; I2 =0%). Thicker EAT was significantly associated with MACEs (pooled relative ratio 1.50, 95% 1.18-1.90, p =0.008). A lower EAT volume is associated with larger infarct size in ST elevated myocardial infarction patients treated with primary PCI (standard mean difference was -5.45, 95% CI -8.10, -2.80; p <0.0001; I2 =0%). In summary, our systemic review and meta-analysis suggest that high EAT is related with a significant increased risk of non-reflow, MACE and decreased infarct size in patients with coronary artery disease treated with PCI. This paradox phenomenon demonstrates that the quality of EAT may play more important role than the solely thickness or volume of EAT.

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