scholarly journals The Effects of Cinnamomum zeylanicum on Lipid Profiles and Histology Via Up-Regulation of LDL Receptor Gene Expression in Hamsters Fed a High Cholesterol Diet

Author(s):  
Seyed Mehrdad Kassaee ◽  
Mohammad Taghi Goodarzi ◽  
Nasim Hayati Roodbari ◽  
Parichehr Yaghmaei
2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Alex Sotolongo ◽  
Yi-Zhou Jiang ◽  
John Karanian ◽  
William Pritchard ◽  
Peter Davies

Objective: One of the first clinically detectable changes in the vasculature during atherogenesis is the accumulation of cholesterol within the vessel wall. Hypercholesterolemia is characterized by dysfunctional endothelial-dependent vessel relaxation and impaired NOS3 function. Since DNA methylation at gene promoter regions strongly suppresses gene expression, we postulated that high-fat/high-cholesterol diet suppresses endothelial NOS3 through promoter DNA methylation. Methods: Domestic male pigs were fed control diet (CD) or isocaloric high fat and high cholesterol diet (HC; 12% fat and 1.5% cholesterol) for 2, 4, 8 or 12 weeks prior to tissue collection. Furthermore, to determine the effects of risk factor withdrawal, an additional group of swine received HC for 12 weeks and then CD for 8 weeks; a control group received HC continuously for 20 weeks. Endothelial cells were harvested from common carotid aorta. In parallel in vitro studies, cultured human aortic endothelial cells (HAEC) were treated with human LDL, GW3956 (LXR agonist) and RG108 (DNA methyltransferase [DNMT] inhibitor). In cells from both sources, DNA methylation at the NOS3 promoter was measured using methylation specific pyro sequencing, and endothelial gene expression was measured using RT PCR. Results: HC diet increased plasma cholesterol level from 75 mg/dl on CD to a plateau of about 540 mg/dl within 2 weeks. Endothelial NOS3 expression was significantly reduced (71±9 % of CD) after 4 weeks of HC, a level sustained at subsequent time points. Withdrawal of HC for 8 weeks did not recover NOS3 expression. After 12-week HC, the NOS3 promoter was hypermethylated. Withdrawal of HC did not reverse NOS3 promoter methylation. In vitro treatment of HAEC with human LDL (200 mg/dl total cholesterol) or GW3956 (5μM) suppressed NOS3 mRNA to 50% and 30% respectively, suggesting that LXR/RXR is involved in suppression of NOS3. Nitric oxide production was consistently suppressed by GW3959. Both could be reversed through inhibition of DNMTs by RG108. Conclusions: DNA methylation and LXR/RXR pathway can mediate the HC-suppression of endothelial NOS3. The study identifies novel pharmaceutical targets in treating endothelial dysfunction. Crosstalk between these pathways is under investigation.


2005 ◽  
Vol 25 (6) ◽  
pp. 597-606 ◽  
Author(s):  
Tae-Youl Ha ◽  
Songyi Han ◽  
Sung-Ran Kim ◽  
In-Hwan Kim ◽  
Hyun-Yu Lee ◽  
...  

Inflammation ◽  
2007 ◽  
Vol 30 (3-4) ◽  
pp. 105-117 ◽  
Author(s):  
Xiaoyan Dai ◽  
Xiang Ou ◽  
Xinrui Hao ◽  
Dongli Cao ◽  
Yaling Tang ◽  
...  

1989 ◽  
Vol 67 (8) ◽  
pp. 968-973 ◽  
Author(s):  
Koichiro Takagi ◽  
Jerome F. Strauss III

Low density lipoprotein (LDL)-carried cholesterol is a primary substrate for steroid hormone synthesis by luteinized human granulosa cells. Chorionic gonadotropin and 8-bromo-cAMP both increase LDL receptor levels in granulosa cells by stimulating accumulation of the receptor mRNA. LDL and 25-hydroxycholesterol reduce LDL receptor expression, but this suppressive effect is partially overcome by 8-bromo-cAMP. Using fusion gene constructs containing the LDL receptor gene promoter transfected into JEG-3 cells, a cyclic AMP responsive enhancer could not be identified in the LDL receptor gene upstream promoter in transfection studies. We suggest that the LDL receptor gene in human steroidogenic cells is under negative control by a sterol effector, but that a cyclic AMP triggered process overcomes, to some extent, the sterol-mediated suppression. The detailed mechanisms by which sterol and cyclic AMP modulate LDL receptor gene expression remain to be elucidated.Key words: low density lipoproteins, low density lipoprotein receptors, cholesterol, steroidogenesis, gonadotropins.


2015 ◽  
Vol 6 (2) ◽  
pp. 492-500 ◽  
Author(s):  
Seung-Min Lee ◽  
Hye Won Han ◽  
Seung Yun Yim

We sought to evaluate whether a soy milk and fiber mixture could improve high cholesterol diet-induced changes in gut microbiota and inflammation.


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