Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantita-tively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus result in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.
Original Articles|
October 01 1997
Immunohistochemical Study of Prostacyclin-Stimulating Factor (PSF) in the Diabetic and Atherosclerotic Human Coronary Artery
Naotaka Sekiguchi;
Naotaka Sekiguchi
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Fumio Umeda;
Fumio Umeda
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Mitsmiori Masakado;
Mitsmiori Masakado
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Yasuhiro Ono;
Yasuhiro Ono
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Toshihiko Hashimoto;
Toshihiko Hashimoto
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Hajime Nawata
Hajime Nawata
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Address correspondence and reprint requests to Dr. Naotaka Sekiguchi, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, Japan.
Diabetes 1997;46(10):1627–1632
Article history
Received:
December 02 1996
Revision Received:
June 05 1997
Accepted:
June 05 1997
PubMed:
9313760
Citation
Naotaka Sekiguchi, Fumio Umeda, Mitsmiori Masakado, Yasuhiro Ono, Toshihiko Hashimoto, Hajime Nawata; Immunohistochemical Study of Prostacyclin-Stimulating Factor (PSF) in the Diabetic and Atherosclerotic Human Coronary Artery. Diabetes 1 October 1997; 46 (10): 1627–1632. https://doi.org/10.2337/diacare.46.10.1627
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