Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: An  in vivo  and  in vitro  study

Lin, Liming; Peng, Feng; Liu, Y.P.; Chai, Dongqi; Ning, Ruo-Bing; Xu, Changsheng; Lin, Jinxiu

doi:10.1016/j.atherosclerosis.2016.06.005

Cited by 37 publications

(25 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest the protective role of vitamin D through regulating the mediators of inflammation and hypoxia signaling against vascular dysfunction, hypertension and CVD. Lin et al[99] reported similar effects of VDR agonists and retinoid X receptor agonists in alleviating atherosclerosis through inhibition of oxidative stress in diabetic mice model (Figure 3). An inverse correlation between the vitamin D level and the stage of coronary atherosclerosis along with the levels of total cholesterol, LDL and triglycerides in women and men over 70 years has been reported [100].…”

Section: Vascular Diseasementioning

confidence: 74%

Role of Vitamin D in Cardiovascular Diseases

Rai

Agrawal

2017

Endocrinology and Metabolism Clinics of North America

122

View full text Add to dashboard Cite

Vitamin D is critical in mineral homeostasis and skeletal health, and plays regulatory role in non-skeletal tissues. Vitamin D deficiency is associated with chronic inflammatory diseases, including diabetes and obesity both being strong risk factors for cardiovascular diseases (CVD). CVD, including coronary artery disease, myocardial infarction, hypertrophy, cardiomyopathy, cardiac fibrosis, heart failure, aneurysm, peripheral arterial disease, hypertension, and atherosclerosis, are major causes of morbidity and mortality worldwide. The association of these diseases with vitamin D deficiency and improvement with vitamin D supplementation suggest its therapeutic benefit. Here, we critically review the recent findings on the association of vitamin D deficiency and CVD.

show abstract

Section: Vascular Diseasementioning

confidence: 74%

Role of Vitamin D in Cardiovascular Diseases

Rai

Agrawal

2017

Endocrinology and Metabolism Clinics of North America

122

View full text Add to dashboard Cite

show abstract

“…In our study the amplitudes of ROR α in liver were attenuated in ApoE-KO mice and ApoE-KO LD/DL mice compared with C57 mice. Diabetes promotes oxidative stress to aggravate atherosclerosis [42], and RXR agonists postponed the atherosclerosis progression [43]. In liver tissue, the acrophase of RXR α was delayed in ApoE-KO LD/DL mice compared with C57 and ApoE-KO mice.…”

Section: Discussionmentioning

confidence: 99%

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

Zhu

Hua

Shang

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

show abstract

“…The cytosolic alkalinization following 1,25(OH) 2 D 3 treatment points to decreased cellular generation of H + or up-regulation of another H + extruding transport protein. For instance, 1,25(OH) 2 D 3 may downregulate the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox and thus H + generating NADPH oxidase activity [40]. Whether 1,25(OH) 2 D 3 modifies NADPH oxidase activity and/or additional carriers in Ishikawa cells, remains, however, elusive.…”

Section: Discussionmentioning

confidence: 99%

1α,25(OH) 2D3 Sensitive Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Ishikawa Cells

Zeng

Zhou

Zhang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)₂D₃), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H⁺ ions and lactate, which is in part accomplished by Na⁺/H⁺ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4. An effect of 1,25(OH)₂D₃ on those transport processes has, however, never been reported. As cytosolic pH impacts on apoptosis, the study further explored the effect of 1,25(OH)₂D₃ on apoptosis and on the apoptosis regulating kinase AKT, transcription factor Forkhead box O-3 (FOXO3A) and B-cell lymphoma protein BCL-2. Methods: In human endometrial adenocarcinoma (Ishikawa) cells, cytosolic pH (pHi) was determined utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na⁺/H⁺ exchanger activity from Na⁺ dependent realkalinization after an ammonium pulse, NHE1 and MCT4 transcript levels using qRT-PCR, NHE1, MCT4, total & phospho AKT, total & phospho-FOXO3A and BCL-2 protein abundance by Western blotting, lactate concentration in the supernatant utilizing a colorimetric enzyme assay and cell death quantification using CytoTox 96^®, Annexin V and Propidium Iodide staining. Results: A 24 hours treatment with 1,25(OH)₂D₃ (100 nM) significantly increased cytosolic pH (pHi), significantly decreased Na⁺/H⁺ exchanger activity, NHE1 and MCT4 transcript levels as well as protein abundance and significantly increased lactate concentration in the supernatant. Treatment of Ishikawa cells with 1,25(OH)₂D₃ (100 nM) further triggered apoptosis, an effect paralleled by decreased phosphorylation of AKT and FOXO3A as well as decreased abundance of BCL-2. Conclusions: In Ishikawa cells 1,25(OH)₂D₃ is a powerful stimulator of glycolysis, an effect presumably due to cytosolic alkalinization. Despite stimulation of glycolysis, 1,25(OH)₂D₃ stimulates slightly but significantly suicidal cell death, an effect presumably in part due to decreased activation of AKT with decreased inhibition of pro-apoptotic transcription factor FOXO3A and downregulation of the anti-apoptotic protein BCL-2.

show abstract

Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: An in vivo and in vitro study

Cited by 37 publications

References 41 publications

Role of Vitamin D in Cardiovascular Diseases

Role of Vitamin D in Cardiovascular Diseases

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

1α,25(OH) 2D3 Sensitive Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Ishikawa Cells

Contact Info

Product

Resources

About