Online Archive of University of Virginia Scholarship
Glutamine Metabolism in Atherosclerotic Plaque Stability8 views
Author
Salamon, Anita, Biochemistry and Molecular Genetics - School of Medicine, University of Virginia0000-0002-5708-9494
Advisors
Owens, Gary, Biochemistry and Molecular Genetics, University of Virginia
Abstract
Heart attacks and strokes are late-stage complications of rupture of unstable atherosclerotic plaques. Stable plaques contain stabilizing matrix-producing fibrotic cells, a majority of which are derived from smooth muscle cells (SMCs). The molecular drivers of SMC phenotypic transitions to beneficial fibrotic or destabilizing inflammatory and calcifying phenotypes are unclear. Since atherosclerosis develops over decades, there is extensive interest in identifying dietary alterations that enhance plaque stability. We demonstrate that SMC acquire a fibrotic phenotype dependent on glutamine-derived metabolites supporting both catabolism and collagen synthesis. Moreover, dietary glutamine restriction decreases mortality of mice susceptible to atherosclerotic plaque rupture. Lesions from glutamine-restricted mice are smaller and have increased SMC investment. These findings identify dietary glutamine as a regulator of SMC plasticity and as a driver of cardiovascular mortality, suggesting a new strategy for reducing late-stage complications of atherosclerosis.
Salamon, Anita. Glutamine Metabolism in Atherosclerotic Plaque Stability. University of Virginia, Biochemistry and Molecular Genetics - School of Medicine, PHD (Doctor of Philosophy), 2025-12-02, https://doi.org/10.18130/wxnq-gh27.
