F-18 FDG PET/CT can reflect the synthetic vascular smooth muscle cell activity in the murine model of neointimal hyperplasia

Objectives: Synthetic vascular smooth muscle cells (VSMCs) have critical functions in vascular remodeling disorders including development of atherosclerosis, stent-related re-stenosis, arteriovenous fistula failure and transplanted organ failure. This study aimed to demonstrate the synthetic VSMC activities in the atherosclerotic carotid artery using F-18 FDG PET/CT. Methods: Atherosclerosis was induced in Sprague-Dawley rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections. 28 days later, rats undertook Doppler ultrasonography and F-18 FDG PET/CT. Harvested vessels were subjected to autoradiography, H&E staining, and immunohistochemistry. Antibodies against α-smooth muscle-actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), CD68, myeloperoxidase (MPO), collagen type-III, cyclophilin A (CypA), matrix metallopeptidase-9 (MMP-9), and glucose tranporter-1 (GLUT-1) were used. Results: The atherosclerotic right carotid arteries presented profound luminal narrowing with neointimal hyperplasia and decreased pulse wave velocity assessed by Doppler ultrasonography and histological means. The neointimal hyperplasia areas were made up of α-SMA positive cells with the scanty expressions of SM-MHC. Surrogate markers of synthetic VSMCs such as collagen type III, CypA, and MMP-9 were richly expressed in neointima region. However, neither CD68-immunopositive macrophages nor MPO-immunopositive neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET/CT imaging with subsequent autoradiography showed increased FDG tracer uptake into the atherosclerotic carotid artery. Consistently, the expression of GLUT-1 was markedly increased in neointimal hyperplasia area. Conclusions: F-18 FDG PET/CT can be a potentially useful tool for evaluating synthetic VSMC activities in vascular remodeling disorders.