Increased prostacyclin and thromboxane A2 formation in human varicose veins.
Increased urinary metabolites of the antiaggregatory vasodilator prostacyclin (PGI2) and the proaggregatory vasoconstrictor thromboxane A2 (TXA2) have been reported in deep vein thrombosis; however, the tissue(s) of origin is uncertain. Because little is known about the formation of PGI2 or TXA2 from its common precursor, prostaglandin (PG) endoperoxide H2 (PGH2), by varicose veins, we determined the formation of 6-keto-PGF1 alpha (the stable metabolite of PGI2), TXB2 (the stable metabolite of TXA2), and PGE2. Segments of normal saphenous vein and varicose vein (nine and six patients, respectively) were incubated with 10 microM [14C]PGH2 for 2 min at 37 degrees C; products were separated by thin-layer chromatography. Surface area and mass of normal and varicose vascular segments were 19.5 +/- 0.8 versus 18.8 +/- 0.6 mm2 and 11.6 +/- 1.4 versus 10.7 +/- 0.7 mg, respectively. Formation of 6-keto-PGF1 alpha and TXB2 by the segments of varicose vein was significantly increased over that of normal vein: 157 +/- 14 versus 243 +/- 17 pmole of 6-keto-PGF1 alpha (P less than 0.005) and 22 +/- 3 versus 35 +/- 5 pmole of TXB2 (P less than 0.01). The formation of PGE2 by segments of varicose vein was not significantly different from that of normal vein (201 +/- 9 vs 219 +/- 11, respectively). Deoxyribonucleic acid (DNA) content of normal and varicose vein was 1.69 +/- 0.12 and 1.51 +/- 0.13 mg per gram of tissue, respectively. The data suggest that the increased PGI2 formation may reflect increased activity or content of PGI2 synthase. The increase in TXA2 formation may reflect increased productivity or an increased presence of residual platelets or microemboli.
Haynes
D F
DF
Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Kerstein
M D
MD
Roberts
M P
MP
Bell
W H
WH
Rush
D S
DS
Kadowitz
P J
PJ
McNamara
D B
DB
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014648:Varicose Veins / Q000378:metabolism*
D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol