Platelet stimulation for prostacyclin production in aortic endothelial cell cultures: alteration in diabetes mellitus.
We evaluated the effect of platelets on prostacyclin (PGI2) production in bovine aortic endothelial cell cultures. Human platelet extract significantly stimulated PGI2 production by cultured aortic endothelial cells in a time- and dose-dependent manner, suggesting that platelets contain PGI2-stimulatory activity (PSA). Supernatant fluid separated from platelets activated by collagen also exhibited PSA. The factor(s) causing the PSA of platelets was non-dialysable and heat-stable (56 degrees C for 30 min or 100 degrees C for 3 min), was completely inhibited by trypsin pretreatment, and exhibited an affinity to heparin agarose. Furthermore, gel filtration chromatography showed that the factor(s) responsible for the platelet PSA was eluted at three different peaks with approximate molecular weights of 50,000, 25,000 and 11,000. The PSA of platelet extract from patients with non-insulin-dependent diabetes mellitus (NIDDM) (n = 10) was compared to that from age-matched control subjects (n = 10). Platelet extract from patients with NIDDM stimulated cultured aortic endothelial cells to produce greater amounts of PGI2 than did that from control subjects. These data suggest that the increased PSA of platelets isolated from diabetic patients may contribute to the abnormal interaction between platelets and the vascular wall in diabetic patients.
Inoguchi
T
T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Umeda
F
F
Kunisaki
M
M
Ishii
H
H
Yamauchi
T
T
Nawata
H
H
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002849:Chromatography, Gas; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts; D011464:Epoprostenol