title: Increased shedding of microvesicles from intimal smooth muscle cells in athero-prone areas of the human aorta: implications for understanding of the predisease stage.
abstract: OBJECTIVE
  This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage.
  
  
  METHODS
  Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta.
  
  
  RESULTS
  The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001).
  
  
  CONCLUSIONS
  The present study supports the concept that alterations of the arterial intima occur at the predisease stage.
authors: Institute for Atherosclerosis Research, Russian Academy of Natural Sciences, Moscow, Russia. y.bobryshev@unsw.edu.au
authors: Yuri V
authors: YV
authors: Bobryshev
authors: Murray C
authors: MC
authors: Killingsworth
authors: Alexander N
authors: AN
authors: Orekhov
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001013:Aorta, Thoracic / Q000378:metabolism / Q000648:ultrastructure*; D050197:Atherosclerosis / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000648:ultrastructure*; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure*; D017539:Tunica Intima / Q000378:metabolism / Q000648:ultrastructure*; D055815:Young Adult
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human