Different effects of simvastatin and losartan on cytokine levels in coronary artery disease.
OBJECTIVE
Use of HMG-CoA reductase inhibitors (statins) and angiotensin II type 1 (AT(1)) receptor antagonists reduces the incidence of cardiovascular events. The cytokines macrophage colony-stimulating factor (M-CSF) and transforming growth factor (TGF)-beta may exert proatherogenic and antiatherogenic effects, respectively. In this study, we examined whether treatment with a statin or an AT(1) receptor antagonist alters M-CSF and TGF-beta levels in patients with coronary artery disease.


METHODS
Twenty-seven consecutive patients with coronary artery disease were randomly assigned to the following three treatment groups for 8 weeks: simvastatin 5 mg/day (n = 10); losartan 50 mg/day (n = 9); or control (usual treatment; n = 8). Blood samples were collected before and after treatment.


RESULTS
Clinical characteristics and baseline cytokine levels were comparable among the three groups. Serum levels of M-CSF were significantly decreased only in the simvastatin group (from 403 +/- 71 to 303 +/- 116 pg/mL; p = 0.009). Plasma levels of TGF-beta were significantly increased only in the losartan group (from 5.01 +/- 1.13 to 7.50 +/- 3.83 ng/mL; p = 0.021). Simvastatin decreased serum M-CSF levels independently of changes in total cholesterol or low-density lipoprotein-cholesterol.


CONCLUSIONS
The results of this study indicate that simvastatin decreases serum levels of M-CSF while losartan increases plasma levels of TGF-beta, suggesting that the two drugs may have different anti-atherosclerotic properties.
Sadamatsu
Kenji
K
Department of Cardiology, St Mary's Hospital, Kurume, Japan. k-sadamatsu@umin.ac.jp
Shimokawa
Hiroaki
H
Tashiro
Hideki
H
Seto
Taku
T
Kakizoe
Hiroshi
H
Yamamoto
Kunihiko
K
D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D019808:Losartan / Q000627:therapeutic use*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D008078:Cholesterol, LDL; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D019821:Simvastatin; D019808:Losartan