title: N-terminal rather than full-length osteopontin or its C-terminal fragment is associated with carotid-plaque inflammation in hypertensive patients.
abstract: BACKGROUND
  Hypertensive patients develop carotid atherosclerotic plaques with enhanced inflammation. Full-length osteopontin (OPN-FL), a multifunctional protein whose levels are elevated in association with atherosclerosis, is cleaved by thrombin and matrix metalloproteinases to form a C-terminal and a putatively biologically active N-terminal fragment (OPN-C, OPN-N, respectively). We conducted a study to examine whether plaque inflammation in hypertensive patients corresponds to the expression of OPN or of its cleaved forms or both.
  
  
  METHODS
  We collected 42 carotid plaques from 41 consecutive hypertensive patients during carotid endarterectomy. Plaque tissue was used to measure matrix metalloproteinase-12 (MMP-12) and OPN proteins, and for the classification of plaques as showing low- or high-degree inflammation through histological and immunohistochemical evaluation.
  
  
  RESULTS
  Fifteen highly inflamed plaques and 27 plaques with characteristics of low-grade inflammation were collected. Moderate to heavy staining for OPN characterized 87% of the plaques with high-degree inflammation but only 44% of those with low-degree inflammation, corresponding to the percentages of plaques that were heavily stained for the macrophage marker CD68 (93% versus 26%, respectively, P < 0.01). Western blot analysis showed that the abundance of OPN-FL and OPN-C was comparable in the two groups. However, the abundance of OPN-N was significantly greater in the highly inflamed plaques (median, 3.8 (range, 0.8-7.3) vs. median, 0.9 (range, 0.2-1.5); P = 0.017, respectively). The abundance of MMP-12 was significantly greater in the high- than in the low-degree plaque inflammation group (4.8 (range 1.9-8.8) vs. 1.1 (range 0.3-1.4), respectively; P = 0.03).
  
  
  CONCLUSIONS
  The N-terminal fragment of osteopontin, rather than OPN-FL or OPN-C, is associated with carotid plaque inflammation in hypertensive patients. Future studies should assess whether targeting OPN cleavage could present a new approach to preventing high-risk carotid plaques.
authors: Hypertension Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel. twolak@bgu.ac.il
authors: Talya
authors: T
authors: Wolak
authors: Neta
authors: N
authors: Sion-Vardi
authors: Victor
authors: V
authors: Novack
authors: Georg
authors: G
authors: Greenberg
authors: Gabriel
authors: G
authors: Szendro
authors: Tanya
authors: T
authors: Tarnovscki
authors: Ori
authors: O
authors: Nov
authors: Ilan
authors: I
authors: Shelef
authors: Esther
authors: E
authors: Paran
authors: Assaf
authors: A
authors: Rudich
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D006973:Hypertension / Q000178:diet therapy / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D010446:Peptide Fragments; C582430:osteopontin (1-168), human; D053495:Osteopontin