Visualization of Synthetic Vascular Smooth Muscle Cells in Atherosclerotic Carotid Rat Arteries by F-18 FDG PET

Kisoo Pahk,Jung Woo Byun,Chunsook Kim,Hwa Young Song,Ji Yong Park,Yun-Sang Lee,Jin Chul Paeng,Chanmin Joung,Se-Mi Jung,Won-Ki Kim,Sungeun Kim

doi:10.1038/s41598-017-07073-3

Abstract

Synthetic vascular smooth muscle cells (VSMCs) play important roles in atherosclerosis, in-stent restenosis, and transplant vasculopathy. We investigated the synthetic activity of VSMCs in the atherosclerotic carotid artery using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Atherosclerosis was induced in rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections (2 consecutive days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The atherosclerotic right carotid arteries showed prominent luminal narrowing with neointimal hyperplasia. The regions with neointimal hyperplasia were composed of α-smooth muscle actin-positive cells with decreased expression of smooth muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen type III, cyclophilin A, and matrix metallopeptidase-9 were increased in neointima region. However, neither macrophages nor neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography showed elevated FDG uptake into the atherosclerotic carotid artery. The inner vessel layer showed higher tracer uptake than the outer layer. Consistently, the expression of glucose transporter 1 was highly increased in neointima. The present results indicate that F-18 FDG PET may be a useful tool for evaluating synthetic activities of VSMCs in vascular remodeling disorders.

Highlights

Several molecular imaging studies have reported significant increases of vascular smooth muscle cells (VSMCs) and macrophage populations in neointimal regions in patients with atherosclerosis[4, 5] and in a rabbit model of atherosclerosis[6]
Normal artery was composed of smooth muscle myosin heavy chain (SM-MHC) and α-smooth muscle actin (α-SMA)-positive VSMCs in media (Fig. 2)
The neointimas exhibited significant collagen type III deposition (Fig. 4), which has been shown to be mainly excreted by synthetic VSMCs11

Summary

Introduction

Several molecular imaging studies have reported significant increases of VSMC and macrophage populations in neointimal regions in patients with atherosclerosis[4, 5] and in a rabbit model of atherosclerosis[6]. None of these studies examined VSMC phenotype. Measurement of glucose uptake may be a useful tool for distinguishing synthetic from contractile VSMCs. Partial carotid artery ligation is a well-established technique for generating an animal model of atherosclerosis[9]. We investigated synthetic VSMC activities using F-18 FDG PET in an atherosclerotic rat model of partial carotid artery ligation

Methods

Results

Conclusion