Glutamine supplementation leads to increased atherosclerosis and adventitial cell accumulation in male Apoe-/-mice

Abstract Background and purpose The amino acid glutamine has immunometabolic properties, but its role in atherosclerosis is not well-known. Here, we investigated the effect of dietary supplementation with glutamine on atherosclerosis development and plaque composition using a mouse model of atherosclerosis. Methods and results Male and female Apoe-/- mice received dietary supplementation of glutamine in drinking water while being fed a high cholesterol diet for 8 weeks. Circulating immune cells, atherosclerosis development and plaque composition were evaluated using flow cytometry, morphometric analyses and immunohistochemistry, while plasma metabolites were analysed by mass spectrometry. Male mice fed glutamine had higher plasma glutamine levels, P=0.006, and developed larger atherosclerotic plaques in both the aorta and the aortic root compared to control mice, P= 0.027 and P=0.002, respectively. This was coupled with a larger accumulation of cells in the adventitia surrounding the aorta, including neutrophils and macrophages, P=0.033. Conclusions Dietary supplementation of glutamine leads to increased atherosclerosis development in the aortic root and accumulation of cells in the adventitia of male, but not female Apoe-/- mice. These results implicate glutamine metabolism in the progression of atherosclerosis and highlight the need for more research to investigate a possible sex-specific mechanism, as well as the translatability into human cardiovascular disease.For image description, please refer to the figure legend and surrounding text.