Focal alterations in metabolic capabilities associated with development of cholesterol-induced atheromatous lesions: A quantitative cytochemical study

Abstract

Succinic dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G-6-PDH), and lactic dehydrogenase (LDH) activities were measured in thoracic aorta sections obtained from hypercholesterolemic New Zealand White rabbits in order to characterize metabolic alterations associated with early atheromatous lesion development. Quantitative cytochemical and micrometric techniques were employed to assess enzyme activities within various zones of the vessel wall (intima, inner-, mid-, and outer-tunica media) during lesion development. In aortic sections from control (normocholesterolemic) rabbits, and in nonlesion segments from hypercholesterolemic rabbits, oxidative enzyme activity was uniform and constant among the three zones of the tunica media; activity in uninvolved (nonlesioned) aortic segments excised from cholesterol-fed rabbits did not differ from control levels. In regions of mural lipidosis, however, the intima exhibited markedly elevated activities of SDH, G-6-PDH, and LDH in comparison to the normal rabbit media. From the onset of lesion formation, metabolic alterations (increased G-6-PDH and LDH activities) were evidenced in smooth muscle cells of the inner media. With progressive intimal thickening, increased enzymatic activity was also observed in outer zones of the tunica media. Transmural medial gradients in enzymatic activity were noted in severely lesioned sites. G-6-PDH and LDH activities were greatest in the inner media; SDH activity, however, was greatest in the outer media. The overall data indicate that atheromatous lesion formation is associated with elevated metabolic capabilities within the intima and entire smooth muscle cell population which underlies aortic lesion sites, and that the observed cellular transformations occur only after the onset of mural lipidosis.