Prostacyclin Production in Vascular Endothelium of Patients with Blackfoot Disease

Abstract

Blackfoot disease is an endemic disease of the peripheral vascular system reported more than fifty years ago in the southwest coast of Taiwan, Republic of China.¹ The symptoms are similar to those of the Buerger’s disease or thromboangiitis obliterans.² It is characterized pathologically by intravascular clot formation and inflammation of the vascular wall, which lead to partial or complete occlusion of the vessels involved.³ The area distributed by the diseased vessel then becomes discolored and gangrenous. The lesion often occurs on the lower extremities, hence the name Blackfoot disease.⁴ Other findings include pigmentation, atherosclerosis and a high level of high density lipoprotein (HDL), but a low level of low density lipoprotein (LDL).^2,5 According to the statistics, 97% of Blackfoot disease patients will end up with either surgical amputation or natural disjointment due to gangrene.⁶ After almost thirty years of investigations, no specific treatment has been found. The primary cause of Blackfoot disease still remains elusive despite some intensive studies.^7,8 Chen et al.⁹ reported that the artesian well water of endemic areas contained high concentrations of arsenic (0.1–0.35 ppm). Lu and Ling⁸ also found that ergotamine compounds were unusually high in level in the artesian well water. Both groups of investigators proposed that high concentrations of arsenic and ergotamine compounds in the drinking water in the endemic areas might be the main cause of Blackfoot disease. However, the installation of new water supply and drainage system since 1960 in the endemic areas has not eradicated or significantly reduced the incidence of the disease.¹⁰ In the present report, study of prostaglandins, particularly on 6-keto-PGF_1α and thromboxane B₂ (TXB₂), the stable natural metabolic intermediates of prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) respectively, had been carried out among the patients. PGI₂ is an important factor in platelet anti-aggregation and blood vessel dilatation, and plays an important role in the prevention of atherosclerosis and arterial thrombosis.¹¹ TXA₂ exerts opposite physiological effects of PGI₂. The enzyme activities of prostacyclin synthase, the prime enzyme for the synthesis of PGI₂, and 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH), the enzyme involved in the conversion of PGI₂ to an inactive form 15-OH-PGI₂, were also studied. The aim is to determine whether there is any change in PGI₂ and TXA₂ metabolism in Blackfoot disease patients.