Focal differences in bioenergetic metabolism of atherosclerosis-susceptible and -resistant pigeon aortas

Abstract

To test the hypothesis of altered energy production in aortic sites predisposed to lesion formation, both coupled oxidative phosphorylation (evaluated from P/O ratios) and control of the energy-linked (ATP) NADH transhydrogenase were examined in muscular cushions at the celiac artery bifurcation. Comparisons were made between atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons at ages up to early atherogenesis in WC (1 day to 6 months of development). From 1 day to 12 weeks of age, mitochondria from cushions of both breeds tightly coupled phosphorylation to the oxidation of either β-hydroxybutyrate or succinate. However, by 6 months of age, WC celiac cushions had significantly ( P < 0.05) lower P/O ratios than the SR cushions with either substrate, suggesting uncoupled respiratory-chain phosphorylation. Aortic submitochondrial A-particles from celiac cushions of susceptible pigeons showed no ATP regulation of NADH transhydrogenation at 6 weeks and subsequent ages. This defect is believe to enhance lipid biosynthesis and may be involved in exacerbation of the biochemical arteriopathy in WC. These findings are discussed in terms of relationships between oxidative energy production, lipid accumulation, hypoxic stress, and atherosclerotic involvement.