Systemic changes in arginase and arginine metabolism in a model of atherosclerosis: a comparison of apoE−/− and C57 mice

Abstract

Increased arginase activity is implicated in cardiovascular pathogenesis. Therefore we studied systemic changes in arginase and arginine metabolism in a model of atherosclerosis. ApoE−/− and C57 mice were placed on 45 or 60% fat diets for 2 months. Results showed increased circulating arginase activity with no difference between 45% (14-fold) and 60% (16-fold) fat diet in the apoE−/−. There was a mild increase in the C57 with 45% fat (2.4-fold) and a large increase due to 60% (19-fold). In the plasma, circulating arginine was reduced in the apoE−/− and showed a decreasing trend in the C57. The plasma arginine/ornithine ratio was significantly decreased in all groups that showed profound increased plasma arginase activity. Markers of tissue (LDH) and liver (ALT) injury were markedly elevated in mice with increased arginase activity. Interestingly, blood cell gene expression in the apoE−/− fed 60% fat showed an 11-fold increase in arginase II (AII) and no increase in arginase I (AI). Tissue gene expression showed increased AI (20- 5.5-fold) and AII (14– 19-fold) in aorta and heart respectively in 60% fat apoE−/− (45% to be completed) with no increase in C57. In conclusion, increased circulating arginase activity and reduced arginine are likely the result of liver and/or tissue injury. Increased arginase gene expression in the blood and tissue (apoE−/− only) are likely associated with the development of atherosclerosis.