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Webinar Featuring Art Yurdagul, Ph.D.

August 7, 2025 1:00 PM - 2:00 PM (EDT)

Description

Please join us for our next webinar featuring Art Yurdagul, Ph.D.,  Assistant Professor, at LSU Health Shreveport. The title of his talk is "Impaired Putrescine Synthesis Drives Smooth Muscle Cell Dedifferentiation and Worsens Features of Plaque Instability"

Abstract: Despite significant advances in diagnosis and treatment, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. While most atherosclerotic plaques remain asymptomatic, a subset of unstable plaques can lead to myocardial infarction or sudden death. Plaque instability is partly driven by vascular smooth muscle cell (vSMC) dedifferentiation from a contractile state to phenotypes resembling fibroblasts, adipocytes, osteoblasts, and macrophages. However, the mechanisms underlying vSMC dedifferentiation have yet to be fully resolved. Interestingly, phenotypic modulation of vSMCs has been linked to alterations in amino acid metabolism. The conversion of the amino acid ornithine into putrescine is rate-limited by ODC1, and our new data identify a crucial role for ODC1-dependent putrescine synthesis in vSMC differentiation. Human carotid endarterectomies grouped into stable and unstable atherosclerosis based on the presence or absence of intraplaque hemorrhage showed reductions in ODC1 expression and putrescine levels. We next conducted RNA sequencing of human coronary vSMCs transfected with ODC1 siRNA and identified pathways related to contractility as being downregulated in a myocardin-dependent manner, which was associated with a transcriptional signature resembling unstable atherosclerosis. For the first time, we also demonstrate that SMC-specific ODC1 deletion (Odc1fl/fl TaglnCre+/-) and putrescine deficiency drive vascular remodeling and atherosclerosis. Altogether, our data show that a reduction in putrescine biosynthesis drives vSMC phenotypic modulation and a loss of myocardin-dependent contractility-related genes, and point to restoring putrescine as a treatment for atherosclerosis progression and plaque instability.

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Contact Information

North American Vascular Biology Organization
Name: Bernadette Englert
Phone: (301) 760-7745
Email: bernadette@navbo.org
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