Dietary Pine Bark Extract Reduces Atherosclerotic Lesion Development in Male ApoE-Deficient Mice by Lowering the Serum Cholesterol Level

2009 ◽  
Vol 73 (6) ◽  
pp. 1314-1317 ◽  
Author(s):  
Masao SATO ◽  
Yasuna YAMADA ◽  
Hiromi MATSUOKA ◽  
Sawako NAKASHIMA ◽  
Tomoyasu KAMIYA ◽  
...  
Keyword(s):  
Cholesterol Level ◽  
Serum Cholesterol ◽  
Serum Cholesterol Level ◽  
Atherosclerotic Lesion ◽  
Pine Bark ◽  
Bark Extract ◽  
Lesion Development ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Development

Deficiency in TDAG51 Decreases Atherosclerotic Lesion Development in ApoE-Deficient Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3940-3940
Author(s):  
Gazi S. Hossain ◽  
Ji Zhou ◽  
Kenneth Maclean ◽  
Sarka Lhotak ◽  
Sudesh K. Sood ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Atherosclerotic Lesion ◽  
Double Knockout ◽  
Lesion Development ◽  
Ppar Γ ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Development

Abstract T-cell death associated gene 51 (TDAG51) is a pro-apoptotic gene that can be induced by endoplasmic reticulum (ER) stress agents, including homocysteine, tunicamycin, thapsigargin or dithiothreitol. Our previous studies have demonstrated that transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion and promoted detachment-induced programmed cell death (PCD). In support of these in vitro findings, we have further shown that TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apolipoprotein E (apoE)-deficient mice fed hyperhomocysteinemic diets, compared to mice fed control diet. We designed the current study to investigate the effect of TDAG51 deficiency in the development and progression of atherosclerosis. To assess in vivo significance of TDAG51 on atherosclerosis, we have crossed TDAG51-deficient mice with apoE-deficient mice to obtain double knockout mice. Our findings have demonstrated that TDAG51/apoE-deficient mice have a significant decrease in atherosclerotic lesion area, compared to age- and sex-matched apoE-deficient mice. Total plasma cholesterol and triglycerides as well as lipoprotein profiles were similar in both groups. However, TDAG51/apoE-deficient mice presented with increased hepatic steatosis. Further, a significant upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), a transcription factor required for adipose tissue formation, was demonstrated in TDAG51-deficient mouse embryonic fibroblasts (MEFs), compared to control wildtype MEFs. Interestingly, earlier studies in mice have reported that overexpression of PPAR-γ decreases atherosclerotic lesion development and increases hepatic steatosis - a phenotype similar to that observed in the mouse deficient in both apoE and TDAG51. Collectively, these findings provide evidence that TDAG51 mediates atherosclerotic lesion development and hepatic steatosis through a mechanism involving PPAR-γ.

Abstract 3693: Early Growth Response Gene-1 Deficiency In Bone-marrow-derived Cells Reduces Macrophage Accumulation And Atherosclerotic Lesion Formation In A Hyperlipidemic Mouse Model

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michael R Preusch ◽  
Claudia Albrecht ◽  
Gotz Hofmann ◽  
Erwin Blessing ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Atherosclerotic Lesion ◽  
Lesion Development ◽  
Early Growth Response ◽  
Atherosclerotic Lesions ◽  
Early Growth Response Gene ◽  
Bone Marrow Derived Cells ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Development ◽  
Macrophage Accumulation

Early growth response gene-1 (Egr-1), a prototype of a family of zinc-finger transcription factors, is a master regulator of many genes which play important roles in cardiovascular diseases. Within atherosclerotic lesions Egr-1 is expressed in several cell types, such as smooth muscle cells, endothelial cells and monocytes/macrophages. Since macrophages play a pivotal role in atherosclerotic lesion development, this study investigated the effects of Egr-1-deficiency within bone-marrow derived cells on the development of atherosclerosis in a hyperlipidemic mouse model. Therefore we transplanted bone-marrow from Egr-1 deficient mice and wild type controls into lethally irradiated low-density lipoprotein receptor deficient mice. After 20 weeks on a western diet atherosclerotic lesions within the aortic sinus and gene expression of inflammatory genes in the aortas of the recipients were evaluated. Mice receiving Egr-1 deficient bone-marrow had less atherosclerotic lesion development compared with mice receiving wild type bone-marrow (318 736 ± 98 910μm 2 vs. 404 539 ± 92 408μm 2 , p<0.05). The size of the necrotic core within the lesions was also reduced. Immunohistochemistry revealed that mice receiving Egr-1 deficient bone-marrow had less macrophages in comparison to controls. Gene expression analysis in the aortas of the mice demonstrated reduced expression of Vascular Cell Adhesion Molecule (VCAM-1), an important adhesion molecule during the development of atherosclerosis. These results were validated with in vitro studies where Egr-1-deficient peritoneal macrophages revealed less VCAM-1 mRNA expression after stimulation with lipopolysaccharide in comparison to wildtype macrophages. This study demonstrates that bone-marrow derived Egr-1 promotes macrophage accumulation and atherosclerotic lesion development possible over an increased expression of VCAM-1.

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