title: Low Osteopontin N-Terminal Fragment and Carotid Plaque Stability Associated with Statin or Antiplatelet Therapy.
abstract: BACKGROUND
  Full-length osteopontin (OPN-FL), whose levels are elevated in association with atherosclerosis, is cleaved by thrombin, resulting in the formation of a putatively biologically-active N-terminal cleavage product (OPNN). This study addresses the hypothesis that statin and antiplatelet therapy in hypertensive patients specifically reduces OPN-N, rather than OPN-FL, in carotid plaques.
  
  
  METHODS
  Seventy-four carotid plaques were collected from patients who underwent carotid endarterectomy (CEA). Plaque tissue was used to measure OPN proteins and for histological and immunohistochemical characterization.
  
  
  RESULTS
  There were 22 statin-negative and 52 statin-treated patients. In the carotid plaque, immunohistochemical staining for macrophages was higher in statin-negative vs. statin-treated patients (high CD68 immunostaining was in 61.9 vs. 28.6%, p=.03, respectively). OPN-FL staining had a similar trend, but without statistical significance (78.7 vs. 47.8%, p=.08, respectively). Western blot analysis of plaque OPN-FL showed that statin treatment was not associated with significant alteration of its abundance, but with a significantly lower plaque content of OPN-N [median 0.08 (IQR 0.05-1.01) vs. 0.81 (IQR 0.27-2.86), respectively, p=.015]. Comparable pattern of association between OPN proteins and antiplatelet therapy was found: the abundance of OPN-FL was not different in plaques from untreated or treated patients, while the abundance of OPN-N was significantly reduced in antiplatelet treated vs. non-treated patients [0.08, (IQR 0.05-0.66) vs. 0.89, (IQR 0.13-1.94), p=0.004].
  
  
  CONCLUSIONS
  The effect of anti-atherosclerotic treatment on carotid plaques of hypertensive patients more readily associates with OPN-N than with OPN-FL expression, suggesting that anti-atherosclerotic treatment including statins and antiplatelet drugs modulates the "OPN system".
authors: Rachel
authors: R
authors: Hamias
authors: Liobov
authors: L
authors: Volvich
authors: Esther
authors: E
authors: Paran
authors: Neta
authors: N
authors: Sion-Vardi
authors: Victor
authors: V
authors: Novack
authors: Gabriel
authors: G
authors: Szendro
authors: George
authors: G
authors: Greenberg
authors: Assaf
authors: A
authors: Rudich
authors: Hypertension Unit Soroka University Medical Center, and Ben-Gurion University of the Negev P.O. Box 151 Beer-Sheva 84101, Israel. twolak@bgu.ac.il.
authors: Talya
authors: T
authors: Wolak
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000378:metabolism; D016894:Endarterectomy, Carotid / Q000379:methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D053495:Osteopontin / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D053495:Osteopontin; D013917:Thrombin