IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice.
OBJECTIVE
Whereas growth factors, via their ability to stimulate vascular smooth muscle cell (VSMC) proliferation and migration, have been thought to play a permissive role in atherosclerosis initiation and progression, the role of insulin-like growth factor-1 (IGF-1) is unknown. Here we report for the first time that IGF-1 infusion decreased atherosclerotic plaque progression in ApoE-deficient mice on a Western diet.


RESULTS
ApoE-null mice (8 weeks) were infused with vehicle or recombinant human IGF-1 and fed a high-fat diet for 12 weeks. Analysis of aortic sinuses revealed that IGF-1 infusion decreased atherosclerotic plaque progression and macrophage infiltration into lesions. Furthermore, IGF-1 decreased vascular expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, reduced aortic superoxide formation and urinary 8-isoprostane levels, and increased aortic pAkt and eNOS expression and circulating endothelial progenitor cells, consistent with an antiinflammatory, antioxidant, and prorepair effect on the vasculature.


CONCLUSIONS
Our data indicate that an increase in circulating IGF-1 reduces vascular inflammatory responses, systemic and vascular oxidant stress and decreases atherosclerotic plaque progression. These findings have major implications for the treatment of atherosclerosis.
Sukhanov
Sergiy
S
Cardiology Section, Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave, SL-48, New Orleans, LA 70112, USA.
Higashi
Yusuke
Y
Shai
Shaw-Yung
SY
Vaughn
Charlotte
C
Mohler
Jessica
J
Li
Yangxin
Y
Song
Yao-Hua
YH
Titterington
Jane
J
Delafontaine
Patrick
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001057:Apolipoproteins E; D004041:Dietary Fats; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D007334:Insulin-Like Growth Factor I; D015237:Dinoprost; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt