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Open Access | 10.1172/jci.insight.165713
1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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1Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, United States of America
2School of Medicine, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
3Department of Surgery, Ochsner Medical Center, New Orleans, United States of America
4School of Medicine, University of Missouri at Columbia, Columbia, United States of America
5Veterinary Sciences, Louisiana State University Cardiovascular Center of Excellence, New Orleans, United States of America
6Department of Cardiology, Tulane University School of Medicine, New Orleans, United States of America
7Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, United States of America
8University of Missouri at Columbia, Columbia, United States of America
9Department of Medicine, Tulane University School of Medicine, New Orleans, United States of America
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Published January 5, 2023 - More info
Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque’s fibrous cap thickness, and reduced necrotic core, macrophage content, and cell apoptosis consistent with promotion of a stable plaque phenotype. IGF-1 reduced circulating triglycerides, markers of systemic oxidative stress and CXCL12 chemokine levels. We used spatial transcriptomics (ST) to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. ST analysis shows that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque macrophages, suggesting possible involvement of these molecules in IGF-1’s effect on atherosclerosis. Thus, IGF-1 reduced coronary plaque burden and promoted features of stable plaque in a pig model, providing support for consideration of clinical trials.