Effects of Vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells.
Vitamin D analogs provide survival benefit for chronic kidney disease patients with cardiovascular complications. Activation of smooth muscle cells plays a role in cardiovascular diseases. It is not known how Vitamin D analogs modulate gene expression in smooth muscle cells. In this study, DNA microarray technology was used to assess the gene expression profile in human coronary artery smooth muscle cells treated with 0.1microM 1alpha,25-dihydroxyvitamin D3 (calcitriol) or paricalcitol (an analog of calcitriol) for 30 h. The effects of calcitriol and paricalcitol were similar. A total of 176 target genes were identified with 115 up-regulated and 61 down-regulated genes in the paricalcitol group. Target genes fall into various categories including cell differentiation/proliferation. Real-time RT-PCR analysis demonstrated that paricalcitol dose- and time-dependently regulated the expression of IGF1, WT1 and TGFbeta3, three genes known to modulate cell proliferation. Paricalcitol also down-regulated the expression of natriuretic peptide precursor B and thrombospondin 1. Both drugs inhibited cell proliferation in a dose-dependent manner. This study identified genes not previously known to be regulated by VDR, providing insight into understanding the role of VDR on regulating smooth muscle cell growth, thrombogenicity, fibrinolysis and endothelial regeneration.
Wu-Wong
J Ruth
JR
Abbott Laboratories, R4CM, AP52, 200 Abbott Park Rd., Abbott Park, IL 60064, USA. ruth.r.wuwong@abbott.com
Nakane
Masaki
M
Ma
Junli
J
Ruan
Xiaoan
X
Kroeger
Paul E
PE
D002117:Calcitriol / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects; D004872:Ergocalciferols / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D053782:Transforming Growth Factor beta3; D014807:Vitamin D / Q000031:analogs & derivatives*; D014815:Vitamins / Q000494:pharmacology*; D025721:WT1 Proteins / Q000235:genetics
D004872:Ergocalciferols; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D014815:Vitamins; D025721:WT1 Proteins; D014807:Vitamin D; D012313:RNA; C084656:paricalcitol; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol