Etidronate influences growth and phenotype of rat vascular smooth muscle cells.
Bisphosphonates have been reported to exhibit antiarteriosclerotic and anticalcification effects. We investigated the effect of a bisphosphonate, etidronate, on growth and phenotype of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). Etidronate (10 microM) significantly decreased DNA synthesis evaluated by [3H]thymidine incorporation in VSMC cultured without serum, and 1 microM etidronate significantly inhibited DNA synthesis in the presence of 10% calf serum. Etidronate (10 microM) significantly inhibited VSMC proliferation after 72h incubation. Etidronate (100 microM) significantly increased the expression of SM22alpha mRNA and protein in VSMC, while 10 microM etidronate significantly decreased the expression of matrix Gla mRNA. These findings indicate that etidronate inhibits the exaggerated growth of VSMC from SHR, while altering their phenotype from synthetic to contractile one. These effects of etidronate may account for its antiarteriosclerotic action.
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Jin-Zi
JZ
Su
Noboru
N
Fukuda
Hirobumi
H
Kishioka
Wen-Yang
WY
Hu
Katsuo
K
Kanmatsuse
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D012968:Etidronic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D012333:RNA, Messenger; D012968:Etidronic Acid