Molecular responses of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials.
We studied the influence of paclitaxel, eluted from poly(L-lactic acid) (PLLA), on cultured vascular smooth muscle cell (VSMC) proliferation as a model of bioresorbable stent-induced restenosis. We blended paclitaxel in cast PLLA films (P-PLLA), demonstrating controlled release of the drug, then studied VSMC adhesion, proliferation, and gene expression profiles. No difference in cell adhesion was found between P-PLLA and PLLA controls (105 +/- 12% of PLLA controls). However, P-PLLA significantly reduced VSMC proliferation (40 +/- 15% of PLLA controls, p < 0.05). Using cDNA microarray technology, we identified major effects of P-PLLA, including: upregulation of genes related to apoptosis, anti-proliferation and antioxidation; and suppression of cell cycle regulators and cell survival markers. The expression patterns indicate that P-PLLA regulates gene expression and cell functions via new pathways, including receptor tyrosine kinase (RTKs), mitogen-activated protein kinase (MAPKs), and protein kinase (PKs, e.g., PKA) pathways, in addition to the stabilization of polymerized-microtubules.
Nguyen
Kytai Truong
KT
Joint Program in Biomedical Engineering, The University of Texas at Arlington and The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 76019.
Shaikh
Nishat
N
Wawro
Debra
D
Zhang
Sheng
S
Schwade
Nathan D
ND
Eberhart
Robert C
RC
Tang
Liping
L
D020341:Absorbable Implants; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D000975:Antioxidants; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D020869:Gene Expression Profiling; D006083:Graft Occlusion, Vascular; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008422:Materials Testing; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000378:metabolism*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015607:Stents
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D017239:Paclitaxel