Lawrence A Potempa - Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft microdomains

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  Publication Details (including relevant citation   information):

  FASEB   J.

    23, 1806–1816 (2009)


  Emerging   evidence indicates that in addition

  to native   pentameric C-reactive protein (CRP),

  monomeric   CRP (mCRP) also plays an active role in

  inflammation   associated with cardiovascular diseases.

  mCRP   activates endothelial cells, one of the critical

  events in   cardiovascular diseases; however, the underlying

  molecular   mechanisms are incompletely understood.

  Here we   report that association of mCRP with

  human aortic   and coronary artery endothelial cells is

  predominantly   due to membrane insertion rather than

  binding to   the surface proteins FcgammaRs and proteoglycans.

  We identify lipid rafts as the preferential membrane

  microdomains for mCRP anchorage. mCRP

  binding depends on membrane cholesterol content and

  is synergistically mediated by the putative cholesterol

  binding consensus sequence of CRP (aa 35–47) and the

  C-terminal   octapeptide (aa 199–206). Conversely, disrupting

  during   inflammation.

  lipid rafts   with methyl

  treatment of   rabbit thoracic aorta and carotid artery segments

  with nystatin prevented mCRP-induced IL-8

  release. Our data identify mCRP-lipid raft interaction

  as an important mechanism in mediating cellular responses

  to mCRP and lend further support to the

  notion of mCRP regulation of endothelial cell function

  cyclodextrin or nystain

  Address (URL): http://