Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease.
BACKGROUND
Matrix metalloproteinases (MMPs) are critically involved in the development of unstable plaques. Although arteriosclerotic lesions in patients with diabetes mellitus are more unstable than those of nondiabetic subjects, nothing is known about serum levels of MMPs in these patients or about mechanisms to modulate MMP levels. We investigated MMP levels in diabetic and nondiabetic coronary artery disease (CAD) patients and performed a clinical trial to assess the effect of the PPARgamma-activating, antidiabetic thiazolidinedione rosiglitazone on MMP levels in diabetic CAD patients.


RESULTS
In CAD patients, MMP-2, -8, and -9 serum levels were significantly higher in type 2 diabetic subjects compared with age-, sex-, and body mass index-matched nondiabetics. Thirty-nine diabetic patients with CAD were randomized to receive rosiglitazone 4 mg (twice daily) or placebo for 12 weeks. Rosiglitazone treatment, but not placebo, significantly reduced MMP-9 levels already after 2 weeks by -19.6% (-38.3% to 8.6%, P<0.05), and levels remained suppressed until the end of the study. In addition, rosiglitazone significantly decreased serum amyloid A (SAA) and tumor necrosis factor-alpha levels.


CONCLUSIONS
MMP-9 levels are increased in type 2 diabetic patients with CAD, and treatment of these patients with the antidiabetic PPARgamma-activator rosiglitazone significantly reduces MMP-9, tumor necrosis factor-alpha, and SAA serum levels. These data support anti-inflammatory and potential antiatherogenic effects of thiazolidinediones.
Marx
Nikolaus
N
Department of Internal Medicine II-Cardiology, University of Ulm, Germany. nikolaus.marx@medizin.uni-ulm.de
Froehlich
Johannes
J
Siam
Laila
L
Ittner
Jochen
J
Wierse
Gerhard
G
Schmidt
Arnold
A
Scharnagl
Hubert
H
Hombach
Vinzenz
V
Koenig
Wolfgang
W
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications* / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000077154:Rosiglitazone; D000685:Serum Amyloid A Protein; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001053:Apolipoproteins; D015415:Biomarkers; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D000685:Serum Amyloid A Protein; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9