title: Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques.
abstract: OBJECTIVE
  We investigated the role of Valsartan (V) alone or in combination with Simvastatin (S) on coronary atherosclerosis and vascular remodeling, and tested the hypothesis that V or V/S attenuate the pro-inflammatory effect of low endothelial shear stress (ESS).
  
  
  METHODS
  Twenty-four diabetic, hyperlipidemic swine were allocated into Early (n=12) and Late (n=12) groups. In each group animals were treated with Placebo (n=4), V (n=4) and V/S (n=4) and followed for 8 weeks in the Early group and 30 weeks in the Late group. Blood pressure, serum cholesterol and glucose were similar across the treatment subgroups. ESS was calculated in plaque-free subsegments of interest (n=109) in the Late group at week 23. Coronary arteries of this group were harvested at week 30, and the subsegments of interest were identified, and analyzed histopathologically.
  
  
  RESULTS
  V alone or with S reduced the severity of inflammation in high-risk plaques. Both regimens attenuated the severity of enzymatic degradation of the arterial wall, reducing the severity of expansive remodeling. V alone or with S attenuated the pro-inflammatory effect of low ESS.
  
  
  CONCLUSIONS
  V alone or with S exerts a beneficial effect of reducing and stabilizing high-risk plaque characteristics independent of a blood pressure- and lipid-lowering effect.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Yiannis S
authors.initials: YS
authors.lastname: Chatzizisis
authors.forename: Michael
authors.initials: M
authors.lastname: Jonas
authors.forename: Roy
authors.initials: R
authors.lastname: Beigel
authors.forename: Ahmet U
authors.initials: AU
authors.lastname: Coskun
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Baker
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Stone
authors.forename: Charles
authors.initials: C
authors.lastname: Maynard
authors.forename: Ross G
authors.initials: RG
authors.lastname: Gerrity
authors.forename: William
authors.initials: W
authors.lastname: Daley
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
authors.forename: Charles L
authors.initials: CL
authors.lastname: Feldman
authors.forename: Peter H
authors.initials: PH
authors.lastname: Stone
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000473:pathology; D001794:Blood Pressure; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008297:Male; D011817:Rabbits; D012306:Risk; D019821:Simvastatin / Q000494:pharmacology*; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D008055:Lipids; D013777:Tetrazoles; D000068756:Valsartan; D019821:Simvastatin; D014633:Valine
references.citation: Lancet. 2000 Feb 19;355(9204):637-45
references.pmid: 10696996
references.citation: Circulation. 2000 Apr 4;101(13):1586-93
references.pmid: 10747353
references.citation: Med Sci Monit. 2005 Jun;11(6):RA194-205
references.pmid: 15917731
references.citation: Circulation. 2001 Nov 27;104(22):2716-21
references.pmid: 11723025
references.citation: Circulation. 2008 Feb 26;117(8):993-1002
references.pmid: 18250270
references.citation: J Am Coll Cardiol. 2007 Jun 26;49(25):2379-93
references.pmid: 17599600
references.citation: J Clin Endocrinol Metab. 2003 Sep;88(9):4496-501
references.pmid: 12970329
references.citation: Circ Res. 2002 Feb 22;90(3):251-62
references.pmid: 11861412
references.citation: Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):556-63
references.pmid: 17170375
references.citation: Basic Res Cardiol. 2002 Mar;97(2):105-16
references.pmid: 12002257
references.citation: Hypertens Res. 2004 Jul;27(7):517-22
references.pmid: 15302989
references.citation: Circulation. 2005 Nov 22;112(21):3328-36
references.pmid: 16286588
references.citation: Circulation. 2006 Jun 13;113(23):2744-53
references.pmid: 16754802
references.citation: Circ Res. 2005 Feb 18;96(3):368-75
references.pmid: 15653570
references.citation: Hypertension. 2004 Nov;44(5):758-63
references.pmid: 15452025
references.citation: Circulation. 2003 Jul 29;108(4):438-44
references.pmid: 12860915
references.citation: Circulation. 2001 Apr 3;103(13):1740-5
references.pmid: 11282904
references.citation: Circulation. 2004 Aug 24;110(8):1013-20
references.pmid: 15326080
references.citation: Hypertension. 2005 Apr;45(4):545-51
references.pmid: 15723967
references.citation: Arterioscler Thromb Vasc Biol. 2000 May;20(5):1262-75
references.pmid: 10807742
references.citation: Atherosclerosis. 2007 Nov;195(1):39-47
references.pmid: 17224157
references.citation: Am J Cardiol. 2006 Jan 1;97(1):13-6
references.pmid: 16377275
references.citation: J Am Coll Cardiol. 2006 Feb 21;47(4):726-33
references.pmid: 16487836
references.citation: J Am Soc Nephrol. 2007 Aug;18(8):2311-9
references.pmid: 17634441
references.citation: Diabetes. 2001 Jul;50(7):1654-65
references.pmid: 11423488
references.citation: Circulation. 2004 Oct 5;110(14):2060-5
references.pmid: 15451796