A Novel Model of Atherosclerosis in Rabbits Using Injury to Arterial Walls Induced by Ferric Chloride as Evaluated by Optical Coherence Tomography as well as Intravascular Ultrasound and Histology

Abstract

This study aim was to develop a new model of atherosclerosis by FeCl3-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (n = 15) by combination of a cholesterol-rich diet and FeCl3-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (n = 3), 8 weeks (n = 6), and 12 weeks (n = 6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl3. The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time.

Cholesterol Diet Withdrawal Leads to an Initial Plaque Instability and Subsequent Regression of Accelerated Iliac Artery Atherosclerosis in Rabbits

“…The cross-sectional narrowing (CSN) was defined as the extent to which the PA occupied the potential lumen area and was calculated as %CSN =  (PA/IEL area) ×100 [4]. The area of positive staining of alcian blue (an individual component of movat pentachrome staining which stains ground substance), α-actin, RAM-11 and metalloproteinase-9 (MMP-9) was expressed as a percentage of stained area divided by the plaque area of the iliac artery in at least 20–30 high-power fields (20× magnification) of sections of respective group animals throughout the artery length [26], [27]. The lipid composition of the lesion was determined by calculating the percent of the oil red O positive area to the total cross-sectional vessel wall area [28].…”

Iron-Induced Fibrin in Cardiovascular Disease

“…In addition, links have been found to exist between iron body stores, cardiovascular risk factors and hypercoagulability [25, 26]. Moreover, in experimental models the infusion of trivalent iron salts was shown to cause diffused thrombosis [27]. It is a common belief that free blood iron, via the Fenton-like reaction, is responsible for so-called oxidative stress that, in turn, leads to atherosclerosis and related cardiovascular diseases [28].…”

A Novel Rabbit Model for In-Stent Neoatherosclerosis

“…Optical coherence topographic analysis: Assessment of neoatherosclerosis included a determination of the presence of lipids within the stent (Figure 4). As reported previously, [16][17][18] lipids were defined as a diffusely bordered, signal-poor region with rapid signal attenuation. Lipidladen neointima was defined as neointima-containing lipids.…”