Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats.
BACKGROUND
Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1.


OBJECTIVE
This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals.


METHODS
Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days.


RESULTS
At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2).


CONCLUSIONS
Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease.
Blankenberg
F G
FG
Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA. blankenb@leland.stanford.edu
Wen
P
P
Dai
M
M
Zhu
D
D
Panchal
S N
SN
Tait
J F
JF
Post
A M
AM
Strauss
H W
HW
Valantine
H A
HA
D000818:Animals; D001786:Blood Glucose; D018932:Chemokine CCL2 / Q000493:pharmacokinetics; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000276:immunology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000473:pathology; D048909:Diabetes Complications; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000000981:diagnostic imaging* / Q000276:immunology; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000000981:diagnostic imaging; D008297:Male; D011877:Radionuclide Imaging; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose; D018932:Chemokine CCL2