Effect of erythromycin on homocysteine-induced extracellular matrix metalloproteinase-2 production in cultured rat vascular smooth muscle cells.
OBJECTIVE
Several lines of evidence have shown an association between Chlamydia infection and atherosclerosis, but clinical trials of preventive antibiotic (erythromycin) treatment in patients with coronary artery disease have shown conflicting results. Hyperhomocysteinaemia is an independent risk factor of coronary artery disease and causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. In the present study we investigated the effects of erythromycin on the production of homocysteineinduced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells (VSMCs).


METHODS
Effects of different concentration of homocysteine (Hcy) (0-5000 micromol/l) on MMP-2 production, and the effects of different erythromycin concentrations (0-10 mmol/l) on homocysteine-induced MMP-2 production in cultured rat VSMCs were studied using gelatin zymography and Western blotting. The changes of MMP-2 under various treatments for 1, 3 and 5 days were also compared.


RESULTS
Homocysteine (50-1000 mu mol/l) increased the production of MMP-2 significantly in a dose-dependent manner and reduced the production of MMP-2 at a high level (5000 mu mol/l). Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added erythromycin in a dose-dependent manner.


CONCLUSIONS
Homocysteine increased the production of MMP-2 significantly in a dose-dependent manner. Extracellularly added erythromycin decreased homocysteine-induced MMP-2 secretion. The findings of the present study suggested that the beneficial effect of erythromycin on vascular disease processes might be due to its inhibitory effect on the Hcyinduced production of MMP-2 in VSMCs.
Guo
Hangyuan
H
Department of Cardiology, Huayu Hospital, China Medical College, Shaoxing, Zhejiang 312030, China. ghangyuan@hotmail.com
Lee
Jong Dae
JD
Yue
Hong
H
Uzui
Hiroyasu
H
Xing
Yangbo
Y
Wang
Junbo
J
Toyoda
Kiyohiro
K
Geshi
Tooru
T
Ueda
Takanori
T
D000818:Animals; D002478:Cells, Cultured; D004917:Erythromycin / Q000494:pharmacology*; D006710:Homocysteine / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006710:Homocysteine; D004917:Erythromycin; D020778:Matrix Metalloproteinase 2