Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia

Authors

Sergiy Sukhanov, Tulane University School of Medicine, New Orleans, LA
Yusuke Higashi, Tulane University School of Medicine, New Orleans, LA
Tadashi Yoshida, Tulane University School of Medicine, New Orleans, LA
Svitlana Danchuk, Tulane University School of Medicine, New Orleans, LA
Mitzi Alfortish, Tulane University School of Medicine, New Orleans, LA
Traci Goodchild, LSU Health Sciences Center - New Orleans
Amy Scarborough, LSU Health Sciences Center - New OrleansFollow
Thomas Sharp, LSU Health Sciences Center - New Orleans
James S. Jenkins, Ochsner Medical Center, New Orleans, LA
Daniel Garcia, Ochsner Medical Center, New Orleans, LA
Jan Ivey, Ochsner Medical Center, New Orleans, LA
Darla L. Tharp, University of Missouri-Columbia, MO
Jeffrey Schumacher, LSU Health Sciences Center - New Orleans
Zach Rozenbaum, Tulane University School of Medicine, New Orleans, LA
Jay K. Kolls, Tulane University School of Medicine, New Orleans, LA
Douglas Bowles, University of Missouri-Columbia, MO
David Lefer, LSU Health Sciences Center - New OrleansFollow
Patrice Delafontaine, Tulane University School of Medicine, New Orleans, LA

Document Type

Article

Publication Date

1-5-2023

Publication Title

JCI Insight

Abstract

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 showed 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.

PubMed ID

36602878

Volume

8

Issue

4

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Sukhanov, Sergiy; Higashi, Yusuke; Yoshida, Tadashi; Danchuk, Svitlana; Alfortish, Mitzi; Goodchild, Traci; Scarborough, Amy; Sharp, Thomas; Jenkins, James S.; Garcia, Daniel; Ivey, Jan; Tharp, Darla L.; Schumacher, Jeffrey; Rozenbaum, Zach; Kolls, Jay K.; Bowles, Douglas; Lefer, David; and Delafontaine, Patrice, "Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia" (2023). School of Medicine Faculty Publications. 2047.
https://digitalscholar.lsuhsc.edu/som_facpubs/2047
10.1172/jci.insight.165713