title: Activation of human vascular cells decreases their expression of transforming growth factor-beta.
abstract: OBJECTIVE
  Despite pro-fibrotic effects, transforming growth factor (TGF)-β prevents arteriosclerosis by suppressing effector leukocytes and promoting smooth muscle differentiation. However, previous observations of increased TGF-β expression in arteriosclerotic plaques are not consistent with that of an effective protective factor. We investigated the expression, regulation, and responses of TGF-β in human arterial tissues and cells.
  
  
  RESULTS
  The expression of TGF-β by intrinsic vascular cells was lower in arteriosclerotic than non-diseased coronary arteries. Activation of resident and infiltrating leukocytes did not elicit TGF-β production from coronary artery segments in organ culture. Instead, the basal expression of TGF-β by coronary arteries decreased after vessel procurement and ex vivo culture. Activation of cultured smooth muscle cells and endothelial cells with phorbol ester and ionophore also decreased TGF-β expression. Isolated cell types representing those found in the artery wall were all capable of signaling in response to TGF-β, however production of the cytoprotective molecule, interleukin-11 was cell type-dependent and restricted to smooth muscle cells and fibroblasts. Interleukin-11 reduced smooth muscle cell apoptosis to T cell effectors.
  
  
  CONCLUSIONS
  Inflammation and cellular activation diminish the basal expression of TGF-β by quiescent human vascular cells. Induction of interleukin-11 may contribute to the anti-arteriosclerotic actions of TGF-β.
authors.affiliation: Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Lebastchi
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Qin
authors.forename: Salman F
authors.initials: SF
authors.lastname: Khan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Arnar
authors.initials: A
authors.lastname: Geirsson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Kim
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Tellides
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D061207:Calcium Ionophores / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D061207:Calcium Ionophores; C508611:IL11 protein, human; D017370:Interleukin-11; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate