MR molecular imaging of aortic angiogenesis.
OBJECTIVE
The objectives of this study were to use magnetic resonance (MR) molecular imaging to 1) characterize the aortic neovascular development in a rat model of atherosclerosis and 2) monitor the effects of an appetite suppressant on vascular angiogenesis progression.


BACKGROUND
The James C. Russell:LA corpulent rat strain (JCR:LA-cp) is a model of metabolic syndrome characterized by obesity, insulin resistance, hyperlipidemia, and vasculopathy, although plaque neovascularity has not been reported in this strain. MR molecular imaging with alpha(nu)beta(3)-targeted nanoparticles can serially map angiogenesis in the aortic wall and monitor the progression of atherosclerosis.


METHODS
Six-week old JCR:LA-cp (+/?; lean, n = 5) and JCR:LA-cp (cp/cp; obese, n = 5) rats received standard chow, and 6 obese rats were fed the appetite suppressant benfluorex over 16 weeks. Body weight and food consumption were recorded at baseline and weeks 4, 8, 12, and 16. MR molecular imaging with alpha(nu)beta(3)-targeted paramagnetic nanoparticles was performed at weeks 0, 8, and 16. Fasted plasma triglyceride, cholesterol, and glucose were measured immediately before MR scans. Plasma insulin and leptin levels were assayed at weeks 8 and 16.


RESULTS
Benfluorex reduced food consumption (p < 0.05) to the same rate as lean animals, but had no effect on serum cholesterol or triglyceride levels. MR (3-T) aortic signal enhancement with alpha(nu)beta(3)-targeted nanoparticles was initially equivalent between groups, but increased (p < 0.05) in the untreated obese animals over 16 weeks. No signal change (p > 0.05) was observed in the benfluorex-treated or lean rat groups. MR differences paralleled adventitial microvessel counts, which increased (p < 0.05) among the obese rats and were equivalently low in the lean and benfluorex-treated animals (p > 0.05). Body weight, insulin, and leptin were decreased (p < 0.05) from the untreated obese animals by benfluorex, but not to the lean control levels (p < 0.05).


CONCLUSIONS
Neovascular expansion is a prominent feature of the JCR:LA-cp model. MR imaging with alpha(nu)beta(3)-targeted nanoparticles provided a noninvasive assessment of angiogenesis in untreated obese rats, which was suppressed by benfluorex.
Cai
Kejia
K
Washington University, St. Louis, Missouri.
Caruthers
Shelton D
SD
Huang
Wenjing
W
Williams
Todd A
TA
Zhang
Huiying
H
Wickline
Samuel A
SA
Lanza
Gregory M
GM
Winter
Patrick M
PM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001067:Appetite Depressants / Q000494:pharmacology; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating; D005277:Fenfluramine / Q000031:analogs & derivatives / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D020738:Leptin / Q000097:blood; D018810:Magnetic Resonance Angiography; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D053758:Nanoparticles; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001067:Appetite Depressants; D007328:Insulin; D039302:Integrin alphaVbeta3; D020738:Leptin; D014280:Triglycerides; D005277:Fenfluramine; C001584:benfluorex; D002784:Cholesterol