Prostacyclin synthetase activity in human diabetic and nondiabetic vascular tissue.
A decrease in the formation of prostacyclin (PGI2), a potent vasodilating and platelet antiaggregatory substance, has been implicated in the pathogenesis of diabetic vasculopathy. This defect, as well as others, may contribute to imbalances in the thrombo-regulatory system resulting in enhanced platelet aggregability, accelerated atherosclerosis, and subsequent vessel injury. Until recently the major thrust of relevant literature has been directed toward abnormalities in PGI2 quantity or function in vascular tissue from experimentally induced diabetic animal models. For the past 2 years our laboratory has studied prostaglandin metabolism in human diabetic and nondiabetic blood vessels. We determined prostacyclin synthetase (PGI2ase) activity in saphenous veins of diabetic and nondiabetic patients (HSV-D and HSV-ND) undergoing coronary artery bypass grafts and in tibial arteries and tibial veins of diabetic patients (HTA-D and HTV-D) and nondiabetic patients (HTA-ND and HTV-ND) undergoing limb amputation for arterial disease of the lower extremity. Carbon 14-labeled prostaglandin endoperoxide (PGH2) was incubated for 2 minutes with vascular microsomal protein. The products were separated via thin-layer chromatography and quantified by radiochromatographic scan. PGI2ase activity was determined by the formation of 6-keto-PGF1 alpha, the stable breakdown product of PGI2. Results of this study indicate that the microsomal fractions of all vascular tissues studied contain an active PGI2ase capable of forming PGI2; formation is enzymatic, as the amount of product increased with increasing microsomal protein concentration; there is no significant difference in PGI2ase activity between HSV-D and HSV-ND; PGI2ase activity in HTA-D and HTV-D is less than in HSV-D and HSV-ND.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology*; D001808:Blood Vessels / Q000201:enzymology*; D001026:Coronary Artery Bypass; D003577:Cytochrome P-450 Enzyme System; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000201:enzymology; D003925:Diabetic Angiopathies / Q000097:blood / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases; D008875:Middle Aged; D012501:Saphenous Vein / Q000201:enzymology; D013977:Tibia / Q000098:blood supply
D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase