Prostacyclin, thromboxane A2, and prostaglandin E2 formation in atherosclerotic human carotid artery.
Prostaglandin (PG) formation in 16 atherosclerotic human carotid endarterectomy specimens was compared systematically with that of normal carotid artery from seven white pigs and six rhesus monkeys. Prostacyclin (PGI2) formation (picomoles 6-keto-PGF1a/2 min/100 micrograms homogenate protein plus 2 mM glutathione [GSH]) of nonatheromatous intima adjacent proximal (276 +/- 32, mean +/- SEM) or distal (271 +/- 14) to carotid plaque was comparable to that of normal carotid artery from white pig (272 +/- 25, NS) and rhesus monkey (219 +/- 41, NS), and was greater than stenotic intima (156 +/- 17, p less than 0.01), subintimal plaque (168 +/- 14, p less than 0.01), and ulceration (65 +/- 16, p less than 0.01). GSH modulated PGI2 synthesis in all carotid specimens except areas of ulceration (p less than 0.05), but did not restore PGI2 formation in atheromatous fractions to basal level. No detectable arterial thromboxane A2 (TXA2) formation or GSH-dependent PGE2 isomerase activity was observed. The decrement in atherosclerotic carotid artery PGI2 formation was focal (confined to the plaque) and may have been related to loss of effective GSH modulation. These conditions could contribute to a localized imbalance between arterial PGI2 and platelet TXA2 with adverse vascular thromboregulatory consequences.
Rush
D S
DS
Department of Surgery, Tulane University School of Medicine, New Orleans 70112.
Kerstein
M D
MD
Bellan
J A
JA
Knoop
S M
SM
Mayeux
P R
PR
Hyman
A L
AL
Kadowitz
P J
PJ
McNamara
D B
DB
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008253:Macaca mulatta; D011458:Prostaglandins E / Q000096:biosynthesis*; D013552:Swine; D013928:Thromboxane A2 / Q000096:biosynthesis*
D011458:Prostaglandins E; D013928:Thromboxane A2; D011464:Epoprostenol; D005978:Glutathione; D015232:Dinoprostone