Authors: Etoh, Takashi
Hashimoto, Toshihiko
Imamura, Minako
Inoguchi, Toyoshi
Nawata, Hajime
Sekiguchi, Naotaka
Title: Expression of prostacyclin-stimulating factor (PSF) in mononuclear cells of human peripheral blood and THP-1 derived macrophage-like cells, and effects of high glucose concentration
Language (ISO): en
Abstract: Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to development of diabetic angiopathies including that in atherosclerosis. We identified a bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis in cultured aortic ECs. Our previous studies demonstrated that PSF was predominantly expressed by arterial smooth muscle cells (SMCs) and ECs. We immunohistochemically showed that PSF existed in SMCs of human coronary arteries, and PSF staining was markedly reduced in coronary arterial SMCs of patients with type 2 diabetes and/or myocardial infarction. In the present study, we investigated the existence of PSF in human serum, and effects of glucose on serum PSF levels in patients with type 2 diabetes. Immunoblot analysis revealed the presence of PSF in serum, and showed that serum PSF protein concentration was significantly decreased in type 2 diabetic patients. Moreover, there was a significant negative correlation between serum PSF and HbA1c levels in these patients. Using immunohistochemistry, we also showed that PSF was present in serum and in macrophages (Mfs). PSF mRNA was found in Mfs using reverse transcription-polymerase chain reaction (RT-PCR). In addition, effects of high glucose conditions on PSF production in Mfs were examined by Western blotting, and we showed that PSF significantly decreased when Mfs were cultured in high glucose conditions. These results strongly suggested that decreased PSF production might result in decreased production of PGI_2 in atherosclerotic lesions, thus leading to development of diabetic macroangiopathy and atherosclerosis.
Subject Headings: diabetes mellitus
prostacyclin stimulating factor (PSF)
Issue Date: 2005-12-20
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