Comparative effects of rosuvastatin and allopurinol on circulating levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with chronic heart failure.
BACKGROUND
Patients with chronic heart failure (HF) are characterized by alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) levels. However, the impact of hypolipidemic and antioxidant treatment in MMPs and TIMPs is unknown. In the present study, we sought to compare the effects of statins and xanthine oxidase inhibitors on circulating levels of MMPs and TIMPs in patients with chronic HF.


METHODS
Forty-two clinically stable patients with mild to moderate HF were randomized to receive rosuvastatin 10 mg or allopurinol 300 mg daily and followed up for 1 month. Serum levels of MMP-2, -9, TIMP-1, and -2 were measured before and after treatment.


RESULTS
Levels of MMP-2 and -9 were significantly decreased in the rosuvastatin group (from 251±52 ng/ml and 400±206 ng/ml to 215±47 ng/ml and 309±166 ng/ml, p<0.001 and p<0.05 respectively), but not in the allopurinol group. In the rosuvastatin group, TIMP-2 levels were significantly increased (from 85±17 ng/ml to 93±16 ng/ml, p<0.05), while TIMP-1 remained unchanged. In the allopurinol group, no significant changes were observed regarding the levels of TIMPs.


CONCLUSIONS
Short-term rosuvastatin but not allopurinol administration decreases MMP-2 and -9 and increases TIMP-2 levels.
Tousoulis
Dimitris
D
1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece. drtousoulis@hotmail.com
Andreou
Ioannis
I
Tentolouris
Costas
C
Antoniades
Charalambos
C
Papageorgiou
Nikolaos
N
Gounari
Panagiota
P
Kotrogiannis
Iason
I
Miliou
Antigoni
A
Charakida
Marietta
M
Trikas
Athanasios
A
Stefanadis
Christodoulos
C
D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D015415:Biomarkers; D005464:Fluorobenzenes; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000493:Allopurinol; D000068718:Rosuvastatin Calcium; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9