title: Smooth muscle cell apoptosis promotes vessel remodeling and repair via activation of cell migration, proliferation, and collagen synthesis.
abstract: OBJECTIVE
  Although vascular smooth muscle cell (VSMC) apoptosis occurs after vessel injury and during remodeling, the direct role of VSMC death in determining final vessel structure is unclear. We sought to determine the role of VSMC apoptosis in vessel remodeling, medial repair, and neointima formation and to identify the mediators involved.
  
  
  RESULTS
  The left common carotid artery was ligated in SM22α-human diphtheria toxin receptor mice, in which diphtheria toxin treatment selectively induces VSMC apoptosis. Apoptosis induced from day 7 to day 14 after ligation significantly increased neointimal and medial areas, cell proliferation, migration, and vessel size. Neointima formation depended on VSMCs, as VSMC depletion before ligation significantly reduced neointimal area and cellularity. In culture, conditioned media from apoptotic VSMCs promoted VSMC migration, proliferation, and collagen synthesis. Interleukin-6 (IL-6) secretion increased 5-fold and IL-1α 1.5-fold after apoptosis, whereas IL-6 inhibition negated the effect of apoptotic VSMC supernatants on VSMC migration, proliferation, and matrix synthesis.
  
  
  CONCLUSIONS
  Signaling from apoptotic VSMCs directly promotes vessel remodeling, medial repair, and neointima formation after flow reduction. Although lumen size appears to depend on flow, VSMC apoptosis is an important determinant of vessel, medial, and neointimal size after flow reduction.
authors: Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Haixiang
authors: H
authors: Yu
authors: Murray C H
authors: MC
authors: Clarke
authors: Nichola
authors: N
authors: Figg
authors: Trevor D
authors: TD
authors: Littlewood
authors: Martin R
authors: MR
authors: Bennett
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D058426:Neointima / Q000378:metabolism / Q000503:physiopathology
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D003094:Collagen