Prostacyclin and thromboxane A2 formation by atherosclerotic carotid artery: Comparison with normal aorta, saphenous vein, and platelets

Abstract

Prostacyclin (PGI2) and thromboxane A2 (TxA2) formation by whole-tissue segments of nine carotid endarterectomy specimens (CES), five normal aortic specimens (NAS), six saphenous vein specimens (SVS), and four platelet samples were determined by incubation with 10 μmol/L 1-14C-radiolabeled prostaglandin endoperoxide H2 (PGH2), and in other experiments with and without 10 μmol/L of CGS 13080, a TxA2 synthase inhibitor. PGI2 formation (expressed as picomoles 6-keto-PGF1α/2-min incubation per sample) by nonatheromatous proximal intima of CES (307 ± 23, mean ± standard error) and distal intima of CES (260 ± 22) was not statistically different; however, it was greater than atheromatous transitional plaque (159 ± 13 pmol) (p < 0.01) and ulceration regions (140 ± 15 pmol) (p < 0.01) of CES, NAS (204 ± 16 pmol) (p < 0.01), and SVS (165 ± 9 pmol) (p < 0.01). TxA2 formation (expressed as picomoles TxB2/2-min incubation per sample) by CES ulceration (51 ± 2 pmol) was low but greater than proximal (17 ± 2 pmol) (p < 0.01), distal (19 ± 3 pmol) (p < 0.01), and transitional (23 ± 3 pmol) (p < 0.01) regions. TxA2 formation by NAS and SVS was not detected (less than 10 pmol). CGS 13080 inhibited TxA2 formation by CES below the limits of detection. Incubation of 1.9 × 105 intact platelets with 10 μmol/L of PGH2 formed a quantity of TxA2 equal to that of CES ulceration. Platelet homogenization reduced TxA2 formation (p < 0.01), demonstrating the sensitivity of TxA2 synthase activity to experimental conditions and the requirement for whole-tissue incubation with and without CGS 13080 to confirm its presence. Diminished PGI2 and minimal, but detectable, TxA2 formation by ulcerated regions of CES may partially explain platelet adherence and thrombogenicity at these foci because of imbalance between vasoregulatory eicosanoids.