Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials.
A major complication of coronary stenting is restenosis, often accompanied by inflammatory reactions and smooth muscle cell proliferation. Curcumin has been shown to possess anti-inflammatory and anti-proliferative properties, thus we hypothesize that locally released curcumin by coronary stent would diminish in-stent restenosis. As a first test of this hypothesis, curcumin-eluting PLLA films (C-PLLA) were produced and the anti-inflammatory and anti-proliferative properties were then tested using peritoneal phagocytes and human coronary artery smooth muscle cell (hCASMCs) culture systems. We find that the addition of curcumin reduced phagocyte accumulation and activation on C-PLLA films. On the other hand, C-PLLA significantly reduced the proliferation, but not the adhesion, of hCASMCs. The molecular responses of hCASMCs to C-PLLA were further assessed by cDNA microarray analysis. Curcumin up-regulated genes related to apoptosis and enhanced the expression of anti-proliferative and anti-inflammatory factors, and of antioxidants. Equally important, C-PLLA inhibited the cell cycle progression of adherent hCASMCs. The results suggest that curcumin regulates gene expression and cell function through the protein kinase (PK) and mitogen-activated protein kinase (MAPK) pathways. These results support the use of curcumin to inhibit in-stent restenosis.
Nguyen
Kytai T
KT
Department of Biomedical Engineering, University of Texas at Arlington, 214 Engineering Laboratory Building, 501 W 1st Street, Arlington, TX 76019, USA.
Shaikh
Nishat
N
Shukla
Kajal P
KP
Su
Shih-Horng
SH
Eberhart
Robert C
RC
Tang
Liping
L
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D008297:Male; D008422:Materials Testing; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry; D015607:Stents
D001672:Biocompatible Materials; D004343:Drug Implants; D011091:Polyesters; C033616:poly(lactide); D003474:Curcumin