title: Visualizing TGF-β and BMP signaling in human atherosclerosis: a histological evaluation based on Smad activation.
abstract: The TGF-β superfamily members transforming growth factor-β (TGF-β/Activin) and bone morphogenetic proteins (BMP) have been implicated in the pathogenesis of atherosclerosis. However, their role in human disease remains controversial. In this study we used Smad phosphorylation as a read out for TGF-β and BMP signaling during the initiation, progression and (de)stabilization of human atherosclerotic disease.
  
  
  
  A systematic analysis was performed in 114 peri-renal aortic patches (stained with Movat Pentachrome, H&E, pSmad2, pSmad1,5,8 and PAI-1) covering the entire atherosclerotic spectrum (van Dijk, 2010). Immunostaining against T-cells (CD3) and monocytes and macrophages (CD68) was used to explore a putative association between TGF-β and BMP signaling and vascular inflammation.
  
  
  
  Smad phosphorylation was present within the normal arterial wall in approximately 10% of the endothelial cells and intimal smooth muscle cells. A significant increase in pSmad2 and pSmad1,5,8 positivity was found in non-progressive lesions (>50% positivity). No further increase or decrease was found in the progressive atherosclerotic lesions, vulnerable and stabilized lesions. No association was found between TGF-β and BMP signaling and CD3 and CD68 expression, nor cap thickness.
  
  
  
  Activation of the TGF-β and BMP pathways is an early event in atherosclerotic lesion formation. No significant relationships were found between Smad phosphorylation and vessel wall inflammation or plaque vulnerability.
authors.affiliation: Department of Vascular Surgery, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: van Dijk
authors.forename: C C
authors.initials: CC
authors.lastname: Engels
authors.forename: A F
authors.initials: AF
authors.lastname: Schaapherder
authors.forename: A
authors.initials: A
authors.lastname: Mulder-Stapel
authors.forename: P
authors.initials: P
authors.lastname: Ten Dijke
authors.forename: J F
authors.initials: JF
authors.lastname: Hamming
authors.forename: J H N
authors.initials: JH
authors.lastname: Lindeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001011:Aorta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology; D014015:Tissue Banks; D016212:Transforming Growth Factor beta / Q000032:analysis*; D055815:Young Adult
chemical_list: D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta