title: Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: role of monocyte chemoattractant protein-1.
abstract: OBJECTIVE
  Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms.
  
  
  RESULTS
  We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells.
  
  
  CONCLUSIONS
  These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1-dependent mechanisms.
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: David
authors.initials: D
authors.lastname: Manka
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.). tchatterjee@gru.edu.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Chatterjee
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Stoll
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Basford
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Eddy S
authors.initials: ES
authors.lastname: Konaniah
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Ramprasad
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Bogdanov
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Yaoliang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Andra L
authors.initials: AL
authors.lastname: Blomkalns
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: David Y
authors.initials: DY
authors.lastname: Hui
authors.affiliation: From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
mesh_terms: D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism / Q000637:transplantation; D000273:Adipose Tissue / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D009389:Neovascularization, Pathologic; D010641:Phenotype; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration
chemical_list: D000199:Actins; D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D011973:Receptors, LDL; C544013:alpha-smooth muscle actin, mouse
keywords: adipose tissue; hyperplasia