ABSTRACT
<p><b>OBJECTIVE</b>To investigate the potential role of caveolin-1 (CAV-1) on membrane estrogen receptor (mER) mediated proliferation of endothelial progenitor cells (EPCs).</p><p><b>METHODS</b>Bone marrow (BM)-derived EPCs were cultured. The proliferation of EPCs induced by estradiol (E₂)-BSA in the absence or presence of ICI 182, 780 (a pure ER inhibitor), MβCD and CAV-1 siRNA was determined by [³H]-thymidine incorporation. The expression of CAV-1 was detected by Western blot.</p><p><b>RESULTS</b>Proliferation of EPC peaked after 10(-8) mol/L E₂-BSA culture for 24 h (87.5% increase vs. control), and this effect could be inhibited by estrogen receptor blocker ICI 182, 780, indicating that mER-initiated membrane signaling pathways was involved in the proliferation effect of estrogen on EPC. Both cholesterol depletion and CAV-1 siRNA significantly attenuated E₂-BSA induced [³H]-thymidine incorporation. Western blot result confirmed that cholesterol depletion or CAV-1 siRNA significantly decreased CAV-1 protein expression (-18.6% or -41.2% vs. 10(-8) mol/L E₂-BSA alone).</p><p><b>CONCLUSION</b>Our results suggested that estradiol promoted EPC proliferation through activating CAV-1 pathway.</p>
Subject(s)
Animals , Rats , Caveolin 1 , Allergy and Immunology , Pharmacology , Cell Proliferation , Cells, Cultured , Endothelial Cells , Cell Biology , Metabolism , Endothelium, Vascular , Cell Biology , Metabolism , Estradiol , Metabolism , Rats, Sprague-Dawley , Receptors, Estrogen , Metabolism , Stem Cells , Cell Biology , MetabolismABSTRACT
The aim of the present study was to investigate the effect of ERK on 17beta-estradiol (E(2)) inhibition of vascular smooth muscle cell (VSMC) proliferation in rats after vascular injury. Common carotid artery balloon-injury (Inj) model was established in ovariectomized rats (OVX). Female SD rats were randomly divided into 4 groups: OVX, E(2)+OVX, OVX+Inj, and E(2)+OVX+Inj groups. The thickness of the vessels, the plasma content of NO, and the expression of ERK, phosphorylated ERK as well as eNOS protein were measured. The results showed that compared with OVX, the vessel wall was significantly thickened and the plasma content of NO was significantly decreased in OVX+Inj group. E(2) significantly decreased the vessel thickness but increased the plasma NO content after balloon injury. E(2) inhibited the expression of ERK, phosphorylated ERK and induced the eNOS expression. There is a positive correlation between plasma NO content and eNOS protein expression, while there is a negative correlation between plasma NO content and the thickness of vessel. The plasma NO content and the expression of ERK protein were negatively correlated. These results suggest that E(2) increases the vascular eNOS protein expression and NO release, leading to the inhibition of VSMC proliferation after balloon injury by inhibiting the ERK and phosphorylated ERK protein expression.