Published online before print September 17, 2009, doi: 10.1161/CIRCRESAHA.109.199653
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 21, 2009
Revised on September 3, 2009
Accepted on September 3, 2009
Periadventitial Adipose Tissue Plays a Critical Role in Vascular Remodeling
Minoru Takaoka ;
From the Departments of Cardiovascular Medicine (M.T., D.N., R.N.) and Molecular Research for Vascular Diseases (D.N.), Graduate School of Medicine, The University of Tokyo; Department of Metabolic Medicine (S.K., I.S.), Graduate School of Medicine, Osaka University; Department of Biomaterials (Y.K., Y.T.), Institute for Frontier Medical Sciences, Kyoto University; First Department of Internal Medicine (Y.S.), Nara Medical University; and Department of Cardiovascular Medicine (M.S.), Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
* To whom correspondence should be addressed. E-mail: sata{at}clin.med.tokushima-u.ac.jp.
Rationale: 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.
Methods and 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.
Key words: neointima • adipocyte • periadventitial tissue • smooth muscle cell • adipocytokine