title: Modulation of endothelial cell proliferation by retinoid x receptor agonists.
abstract: One feature that contraindicates the wide therapeutic use of natural retinoids is their adverse effects during systemic use and the lack of receptor selectivity. In contrast, synthetic retinoids are distinguishable from each other on the basis of their partial or exclusive preference in binding and activation of selective retinoid receptors. We examined the inhibitory activities of natural and synthetic retinoids for their ability to reverse basic fibroblast growth factor-induced endothelial cell proliferation. Both the naturally occurring retinoids at nanomolar concentrations reversed basic fibroblast growth factor-induced endothelial cell proliferation. Among the synthetic retinoids tested, retinoic acid receptor/retinoid x receptor pan-agonist AGN 191659 [(E)-5-[2-(5,6,7, 8-tetrahydro-3, 5,5,8,8-pentamethyl-2-naphtyl) propen-1-yl]-2-thiophenecarboxylic acid] and retinoid x receptor pan-agonist AGN 191701 [(E)-2-[2-(5,6,7,8-tetrahydro-3, 5,5,8, 8-pentamethyl-2-naphthyl) propen-1-yl]-4-thiophenecarboxylic acid] at nanomolar concentrations reversed the basic fibroblast growth factor-induced endothelial cell proliferation. Since none of the retinoic acid receptor agonists tested had any effect, the inhibitory effect of AGN 191659 could be attributed to its retinoid x receptor receptor activity. These results suggest that retinoid x receptor agonists may be more selective anti-angiogenic agents due to their ability to inhibit endothelial cell proliferation.
authors.affiliation: University of Texas Health Science Center - Medical School, Department of Internal Medicine/Division of Cardiology, 6431 Fannin, MSB 6.039, Houston, TX 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pakala
authors.forename: C R
authors.initials: CR
authors.lastname: Benedict
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists*
chemical_list: C403783:AGN 191659; D002264:Carboxylic Acids; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013876:Thiophenes; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; C108491:AGN 191701