[Differential effect of vitamin D analogues on the proliferation of vascular smooth muscle cells].
Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. The excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion. The direct effect of calcitriol and vitamin D analogs on the VSMCs proliferation is not clear. In this study we have analysed if calcitriol, Paricalcitol (19-nor-1,25-dihydroxy-vitamin D2) and EB1089 (experimental analog used as anticancerous) modify proliferation and the expression of vitamin D receptor (VDR) gene that is regulated at the transcriptional level by itself in the VSMCs. VSMCs proliferation was analysed by BrdU incorporation and VDR gene expression using RT-PCR. VSMCs proliferation was stimulated when calcitriol was added to the culture. VSMCs proliferation was significantly lower with analogs at the same dose. With regard to the functional study, the expression of VDR gene was upregulated by calcitriol at a concentration of 100 nM. There were no changes in this expression with the analogs. In conclusion, calcitriol, do not modify VSMCs proliferation. Therefore, Paricalcitol could have a minor proliferating effect on the wall of vessels that vitamin D.
Cardús
A
A
Servicio de Nefrología Hospital Universitari Arnau de Vilanova de Lleida Rovira Roure, 80 25198 Lleida.
Gallego
C
C
Muray
S
S
Marco
M P
MP
Parisi
E
E
Aldea
M
M
Fernández
E
E
D000818:Animals; D001011:Aorta / Q000166:cytology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004872:Ergocalciferols / Q000494:pharmacology*; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D014158:Transcription, Genetic / Q000187:drug effects
D004872:Ergocalciferols; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C084656:paricalcitol; D002117:Calcitriol; C078903:seocalcitol