Gene expression profile of the Gs-coupled prostacyclin receptor in human vascular smooth muscle cells.
Migration and proliferation of medial smooth muscle cells (SMC) in the arterial intima contributes to the development of atherosclerotic plaques and restenotic processes after coronary angioplasty. Prostacyclin (PGI2)-mediated stimulation of cyclic adenosine 3'5'-monophosphate (cAMP) signaling is believed to be important for maintaining SMC in a quiescent state. In order to identify new cellular targets of PGI2/cAMP action, we have used microarray screening to examine changes in the transcriptional profile in human vascular SMC in response to exposure to the stable PGI2 mimetic iloprost. We have identified 83 genes with significantly altered expression after iloprost (100 nM) exposure for 6 hr. Fifty-one genes were upregulated, among them stanniocalcin precursor (18.8+/-2.7), zinc finger transcription factor (7.8+/-2.0), hyaluronan synthase 2 (6.8+/-1.8), cyclooxygenase 2 (4.7+/-0.8), dual specific phosphatase (3.9+/-0.5) and vascular endothelial growth factor (2.3+/-0.4). Thirty-two genes were reduced, among them cystein-rich angiogenic protein (-14.9+/-1.3), monocyte chemotactic protein 1 (-7.4+/-1.1) and plasminogen activator inhibitor PAI-1 (-4.5+/-0.5). By means of semi-quantitative RT-PCR, time-courses of gene expression were established. The present study identified genes not hitherto recognized to be targets of PGI2 action, providing further insight into its cAMP-mediated effects on SMC growth, migration and matrix secretion.
Meyer-Kirchrath
Jutta
J
Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum, Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
Debey
Svenja
S
Glandorff
Christian
C
Kirchrath
Lutz
L
Schrör
Karsten
K
D001161:Arteriosclerosis / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D044006:Receptors, Epoprostenol / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D044006:Receptors, Epoprostenol; D011464:Epoprostenol; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D016285:Iloprost