Effect of rosiglitazone treatment on plaque inflammation and collagen content in nondiabetic patients: data from a randomized placebo-controlled trial.
BACKGROUND
Therapeutic strategies to stabilize advanced arteriosclerotic lesions may prevent plaque rupture and reduce the incidence of acute coronary syndromes. Thiazolidinediones (TZDs), like rosiglitazone, are oral antidiabetic drugs with additional antiinflammatory and potential antiatherogenic properties. In a randomized, placebo-controlled, single-blind trial, we examined the effect of 4 weeks of rosiglitazone therapy on histomorphological characteristics of plaque stability in artery specimen of nondiabetic patients scheduled for elective carotid endarterectomy.


RESULTS
A total of 24 nondiabetic patients with symptomatic carotid artery stenosis were randomly assigned to rosiglitazone (4 mg BID) or placebo in addition to standard therapy. In this population of nondiabetic patients, rosiglitazone treatment did not significantly change fasting blood glucose, fasting insulin, or lipid parameters. In contrast, rosiglitazone significantly reduced CD4-lymphocyte content as well as macrophage HLA-DR expression in the shoulder region, reflecting less inflammatory activation of these cells by lymphocyte interferon-gamma. Moreover, rosiglitazone significantly increased plaque collagen content (7.7+/-1.6% versus 3.7+/-0.7% of plaque area; P=0.036) compared with placebo, suggesting that TZD treatment may stabilize arteriosclerotic lesions. In addition, rosiglitazone reduced serum levels of 2 inflammatory arteriosclerosis markers: C-reactive protein and serum amyloid A.


CONCLUSIONS
Four weeks of treatment with rosiglitazone significantly reduces vascular inflammation in nondiabetic patients, leading to a more stable type of arteriosclerotic lesion.
Meisner
Franz
F
Department of Thoracic and Vascular Surgery, University of Ulm, Germany.
Walcher
Daniel
D
Gizard
Florence
F
Kapfer
Xaver
X
Huber
Roman
R
Noak
Anja
A
Sunder-Plassmann
Ludger
L
Bach
Helga
H
Haug
Cornelia
C
Bachem
Max
M
Stojakovic
Tatjana
T
März
Winfried
W
Hombach
Vinzenz
V
Koenig
Wolfgang
W
Staels
Bart
B
Marx
Nikolaus
N
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003094:Collagen / Q000378:metabolism*; D003920:Diabetes Mellitus; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D000685:Serum Amyloid A Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000627:therapeutic use
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D007328:Insulin; D000685:Serum Amyloid A Protein; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003094:Collagen; D002097:C-Reactive Protein; D002784:Cholesterol