title: Leptin-dependent and leptin-independent paracrine effects of perivascular adipose tissue on neointima formation.
abstract: OBJECTIVE
  Clinical and experimental evidence suggests that periadventitial adipose tissue may modulate vascular lesion formation. The aim of this study was to determine the role of perivascular leptin expression on neointima formation and to differentiate it from local inflammation and systemically elevated leptin levels.
  
  
  RESULTS
  Increased neointima formation after carotid artery injury was observed in hyperleptinemic, diet-induced obese wild-type mice, but not in leptin-deficient ob/ob mice. High-fat diet was associated with increased leptin expression in visceral adipose tissue (VAT) as well as in perivascular adipose tissue. Perivascular leptin overexpression achieved by adenoviral vectors enhanced intimal cell proliferation and neointima formation in wild-type mice, but not in leptin receptor-deficient mice. Perivascular transplantation of VAT from high-fat diet-induced obese wild-type mice around the carotid artery of immunodeficient mice also promoted neointima formation, without affecting body weight or systemic leptin levels, and this effect was absent, if VAT from ob/ob mice was used. On the contrary, perivascular transplantation of VAT from ob/ob mice fed high-fat diet, characterized by marked immune cell accumulation, promoted neointimal hyperplasia also in the absence of leptin. In vitro, recombinant leptin and VAT-conditioned medium increased human arterial smooth muscle cell proliferation in a (partly) leptin-dependent manner.
  
  
  CONCLUSIONS
  Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity.
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Goettingen, Georg August University of Goettingen, Goettingen, Germany.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Schroeter
authors.forename: Norman
authors.initials: N
authors.lastname: Eschholz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herzberg
authors.forename: Isabel
authors.initials: I
authors.lastname: Jerchel
authors.forename: Maren
authors.initials: M
authors.lastname: Leifheit-Nestler
authors.forename: Frauke S
authors.initials: FS
authors.lastname: Czepluch
authors.forename: Georgios
authors.initials: G
authors.lastname: Chalikias
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D059305:Diet, High-Fat; D006801:Humans; D050152:Intra-Abdominal Fat / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D058426:Neointima / Q000209:etiology*; D009765:Obesity / Q000150:complications
chemical_list: D020738:Leptin