Concurrent treatment with renin-angiotensin system blockers and acetylsalicylic acid reduces nuclear factor kappaB activation and C-reactive protein expression in human carotid artery plaques.
OBJECTIVE
The local renin-angiotensin system (RAS) and cyclooxygenase-2 contribute to the activation of nuclear factor kappaB (NFkappaB) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NFkappaB and CRP within atherosclerotic plaques.


METHODS
Patients undergoing carotid endarterectomy were divided into groups according to treatment (RASb-acetylsalicylic acid [ASA], ASA, RASb, and control). The expression of NFkappaB, CRP, and CD40L was analyzed through Western blots in the obtained plaques.


RESULTS
Plaques from patients treated with the combination of RASb and ASA showed lower expression of NFkappaB (25.4+/-9.8 densitometric units [DU]) than those of the control group (57.6+/-13.2 DU, P=0.03) as well as lower expression of CRP (20.9+/-9.6 DU) than those of the other treatment groups (ASA 86.1+/-13 DU, RASb 88.4+/-31 DU, controls 67.8+/-18.6, P=0.004). A negative expression of NFkappaB was associated with a reduced incidence of symptoms compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031).


CONCLUSIONS
The combined treatment with RASb and ASA decreases the expression of inflammatory markers in atherosclerosis in humans. This study supports the role of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.
Sattler
Katherine J E
KJ
Division of Cardiovascular Diseases, Mayo Clinic Rochester, Rochester, Minn 55905, USA.
Woodrum
Julie E
JE
Galili
Offer
O
Olson
Monica
M
Samee
Saquib
S
Meyer
Fredric B
FB
Zhu
Xiang-Yang
XY
Lerman
Lilach O
LO
Lerman
Amir
A
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D016893:Carotid Stenosis / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D023201:CD40 Ligand; D002097:C-Reactive Protein; D001241:Aspirin