Effect of oral sirolimus therapy on inflammatory biomarkers following coronary stenting.
We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. The mean age of the patients was 56 +/- 13 years, 65% were males and all had clinically manifested ischemia. Serum levels of high sensitivity C-reactive protein (hs-CRP) concentration were determined by chemiluminescence and serum levels of all other biomarkers by ELISA. One group of patients at high risk for ISR received a loading oral dose of 15 mg sirolimus and 5 mg daily thereafter for 28 days after stenting (SIR-G). A control group (CONT-G) was submitted to stenting without sirolimus therapy. The increase in hs-CRP concentration was highest at 24 h after stenting in both groups. A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 +/- 5.0 vs -0.19 +/- 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 +/- 4.3 vs -0.01 +/- 0.7, P = 0.0975). A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 +/- 455 vs +395.2 +/- 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 +/- 708 vs 406.2 +/- 472.1, P = 0.0958). SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 +/- 67.9 vs 5.8 +/- 23.7, P = 0.0025). These findings suggest that the anti-restenotic actions of systemic sirolimus include anti-proliferative effects and modulation of the inflammatory response with inhibition of adhesion molecule expression.
Rosa
W C M
WC
Disciplinas de Cardiologia e Nefrologia, Hospital São Paulo and Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, São Paulo, SP, Brasil. wcmrosa@terra.com.br
Campos
A H
AH
Lima
V C
VC
D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000097:blood* / Q000517:prevention & control*; D023921:Coronary Stenosis / Q000601:surgery; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage*; D015607:Stents
D015415:Biomarkers; D007166:Immunosuppressive Agents; D020123:Sirolimus