Partial purification of serum prostacyclin stimulatory activity by heparin-agarose column; abnormality detected in diabetics.
Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics.
Umeda
F
F
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yamauchi
T
T
Inoguchi
T
T
Nawata
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001786:Blood Glucose / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003956:Dialysis; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006493:Heparin; D006801:Humans; D008297:Male; D008875:Middle Aged
D015121:6-Ketoprostaglandin F1 alpha; D001786:Blood Glucose; D011464:Epoprostenol; D006442:Glycated Hemoglobin; D006493:Heparin