Stimulation of oestrogen receptor-expressing endothelial cells with oestrogen reduces proliferation of cocultured vascular smooth muscle cells.
1. Oestrogen reduces vascular smooth muscle cell proliferation in mouse vascular injury models. Data on the antiproliferative effect of oestrogen in cultured vascular smooth muscle cells (VSMC) are less conclusive than those obtained in whole animal studies. 2. In the present study, we investigated the hypothesis that oestrogen-induced attenuation of VSMC proliferation is facilitated by the presence of endothelial cells (EC) using a coculture system of EC and VSMC. 3. Treatment with a physiological concentration of oestrogen (17beta-estradiol (E2); 100 nmol/L) had no effect on fetal calf serum (FCS)-stimulated DNA synthesis in either A7r5 VSMC or bEnd.3 EC. However, stimulation of bEnd. 3 cells with E2 in a coculture system of bEnd.3 and A7r5 cells reduced FCS-induced DNA synthesis in A7r5 cells by approximately 45%. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME; 100 micromol/L) did not reverse the oestrogen-induced attenuation of DNA synthesis. The antiproliferative effect of E2 may be mediated via either oestrogen receptor (ER) alpha, ERbeta or both because the bEnd.3 cells expressed immunoreactivity for both ER subtypes. 4. These data show that ERalpha- and ERbeta-expressing endothelial cells, which are stimulated with a physiological concentration of oestrogen, release a factor(s) that arrests the proliferation of cocultured VSMC. Oestrogen-induced attenuation of vascular smooth muscle cell proliferation is not prevented by L-NAME, suggesting that a mechanism other than endothelial NO is involved.
Odenlund
Malin
M
Department of Experimental Medical Science, Lund University, Lund, Sweden.
Ekblad
Eva
E
Nilsson
Bengt-Olof
BO
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D004247:DNA / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*
D011960:Receptors, Estrogen; D004958:Estradiol; D004247:DNA; D052250:Nitric Oxide Synthase Type III