Prostaglandin E2 biosynthesis: changes in rabbit aorta and skin during experimental atherogenesis1

• Published in: Journal of lipid research 1976-01, Vol.17 (1), p.46-52
• Main Authors: Berberian, P A, Ziboh, V A, Hsia, S L
• Format: Article
• Language: English
• Subjects: arachidonic acid; cholesterol feeding; intima-media; xanthoma
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)37015-2

The transformation of [1-14C]arachidonic acid into [14C]prostaglandin E2(PGE2) by rabbit aorta and skin was demonstrated by cell-free preparations, and the PGE2 synthetase activity was located mainly in the microsomal fraction (105,000 g pellet) of both tissues. Rabbits fed an atherogenic diet (Purina rabbit chow plus 1% cholesterol and 2% cottonseed oil) developed atheroma in the aortas and skin lesions resembling xanthoma in 6 to 7 months. At the end of this period, increases in the conversion of [1-14C]-arachidonic acid into [14C]PGE2 were observed in microsomal preparations of the intima-media of the aortas (2.5-fold of control) and normal-appearing skin (3.0-fold of control) of the experimental animal. Microsomal preparations of skin lesions particularly had greater ability to form PGE2 (7-fold of control). The level of PGE2 in skin biopsy specimens of the rabbit was studied by gas-liquid chromatography over the first two months of cholesterol feeding. A 2- to 3-fold increase in the level of PGE2 occurred in the first 2 weeks, reaching a peak of 30 ng/mg protein by the 35th day; thereafter, the level gradually declined to the control range at the end of two months. Control groups had a PGE2 level of 2 to 12 ng/mg protein and did not show significant change throughout this period. The results suggest the involvement of PGE2 in atherogenesis, and the possibility of using the skin as an experimental model for the study of atherosclerosis.