Periadventitial adipose tissue plays a critical role in vascular remodeling.
BACKGROUND
Obesity is associated with a high incidence of cardiovascular complications. However, the molecular link between obesity and vascular disease is not fully understood. Most previous studies have focused on the association between cardiovascular disease and accumulation of visceral fat. Periadventitial fat is distributed ubiquitously around arteries throughout the body.


OBJECTIVE
Here, we investigated the impact of obesity on inflammation in the periadventitial adipose tissue and on lesion formation after vascular injury.


RESULTS
High-fat, high-sucrose feeding induced inflammatory changes and decreased adiponectin expression in the periadventitial adipose tissue, which was associated with enhanced neointima formation after endovascular injury. Removal of periadventitial fat markedly enhanced neointima formation after injury, which was attenuated by transplantation of subcutaneous adipose tissue from mice fed on regular chow. Adiponectin-deficient mice showed markedly enhanced lesion formation, which was reversed by local delivery, but not systemic administration, of recombinant adiponectin to the periadventitial area. The conditioned medium from subcutaneous fat attenuated increased cell number of smooth muscle cells in response to platelet derived growth factor-BB.


CONCLUSIONS
Our findings suggest that periadventitial fat may protect against neointimal formation after angioplasty under physiological conditions and that inflammatory changes in the periadventitial fat may have a direct role in the pathogenesis of vascular disease accelerated by obesity.
Takaoka
Minoru
M
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nagata
Daisuke
D
Kihara
Shinji
S
Shimomura
Iichiro
I
Kimura
Yu
Y
Tabata
Yasuhiko
Y
Saito
Yoshihiko
Y
Nagai
Ryozo
R
Sata
Masataka
M
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006965:Hyperplasia; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D052242:Adiponectin; C499919:Adipoq protein, mouse; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D000077214:Becaplermin; D055372:AMP-Activated Protein Kinases