高齢者動脈硬化症の退縮に関する研究（４）中心性陥凹を呈する動脈硬化性病変とｐｅｒｏｘｉｓｏｍｅ　ｐｒｏｌｉｆｅｒａｔｏｒ－ａｃｔｉｖａｔｅｄ　ｒｅｃｅｐｔｏｒｓ　（ＰＰＡＲｓ）発現についての検討

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  • Atherosclerotic regression in the aortas of elderly. (4) Expression of peroxisome proliferator-activated receptors with references of centrally depressed atherosclerotic plaque
  • コウレイシャ ドウミャク コウカショウ ノ タイシュク ニ カンスル ケンキュウ 4 チュウシンセイカンオウ オ テイスル ドウミャク コウカセイ ビョウヘン ト peroxisome proliferator activated receptors PPARs ハツゲン ニ ツイテ ノ ケントウ

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Peroxisome proliferator-activated receptors (PPARs) play an important role in vascular events during progression of atherosclerosis, associated with lipid metabolism, inflammatory response and others. To clarify relationships between the expression of PPARs subtypes and regression, we studied mRNA expression of PPARs subtypes with reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, especially in centrally depressed atherosclerotic plaques (depressed plaque) in the aortas of elderly patients, and proposed morphological feature of atherosclerotic regression. Samples were separated from the depressed plaque, atheromatous plaque, and diffuse intimal thickening (DIT) in the aortas of elderly patients at autopsy and they were analyzed for RT-PCR. The depressed plaques obtained were divided into two parts: depressed area and surrounding elevated area. Total RNA was prepared, using the TRIzol Reagent, and was reverse transcribed using random hexamer primers and Thermoscript kit for RT-PCR. Immunohistochemical analysis was processed for mouse anti-PPARγ antibody, detected by the ABC method. 1) Decreased foam cells were found in the depressed area than in the surrounding elevated area of the depressed plaque. These foam cells were immunohistochemically positive for HAM56 and strong reactivities for PPARγ were found in the nuclei of macrophage-derived foam cells. PPARγ was also detected in the nuclei of endothelial cells and smooth muscle cells. 2) Expressions of PPARα and PPARγ were found in the depressed plaques with RT-PCR. These expressions were found both in the depressed area and the surrounding elevated area without significant differences. 3) PPARγ mRNA expression both in the depressed area and the surrounding elevated area, was greater than in DIT, and was less than in the atheromatous plaque. 4) Expression of PPARγ mRNA was intense and increased in the surrounding elevated area than in the depressed area. 5) A significant increase of PPARγ expression was found in the atheromatous plaque than in the DIT. 6) There was no significant difference of PPARα mRNA expression between the depressed area and the surrounding elevated area. The depressed plaque has been considered to be a morphological characteristic of regression in recent studies. Expression of mRNA for PPARs was detected in the depressed plaque as well as the atheromatous plaque, furthermore, there were different expressions and intensity of PPARs between the depressed area and the surrounding elevated area of the depressed plaque. These findings suggest that the expression of PPARs may be involved not only in the progression of atherosclerosis but also in regression.

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