title: Shear stress-induced mechanotransduction protein deregulation and vasculopathy in a mouse model of progeria.
abstract: BACKGROUND
  A mouse model of progeria derived by insertion of the human mutant LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in the media of the ascending aorta. We hypothesized that high shear stress, in the presence of mutant lamin A, induces this vasculopathy and tried to define the molecular and cellular basis for aortic vasculopathy.
  
  
  METHODS
  Ascending and descending aortas from wild type (WT) and mLMNA+ mice were compared using proteomics, Western blots, PCR and immunostaining. To determine whether high fluidic shear stress, known to occur in the ascending aorta, contributed to the vasculopathy, we exposed descending aortas of mLMNA+ mice, with no apparent vasculopathy, to 75 dynes/cm2 shear stress for 30 minutes using a microfluidic system.
  
  
  RESULTS
  When the mice were one year of age, expression of several mechanotransduction proteins in the ascending aorta, including vimentin, decreased in mLMNA+ mice but no decrease occurred in the descending aorta. High fluidic shear stress produced a significant reduction in vimentin of mLMNA+ mice but not in similarly treated WT mice.
  
  
  CONCLUSIONS
  The occurrence of mutant lamin A and high shear stress correlate with a reduction in the level of mechanotransduction proteins in smooth muscle cells of the media. Reduction of these proteins may contribute over time to development of vasculopathy in the ascending aorta in progeria syndrome.
authors.forename: Minjung
authors.initials: M
authors.lastname: Song
authors.forename: Hong
authors.initials: H
authors.lastname: San
authors.forename: Stasia A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cannon
authors.forename: Donald
authors.initials: D
authors.lastname: Orlic
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D034904:Lamin Type A; D040542:Mechanotransduction, Cellular; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011371:Progeria / Q000378:metabolism* / Q000473:pathology*; D011498:Protein Precursors / Q000378:metabolism; D013314:Stress, Mechanical; D014652:Vascular Diseases / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007381:Intermediate Filament Proteins; D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A