Beta-adrenergic receptor regulation of growth factor protein levels in human choroidal endothelial cells.
Remodeling of the choroidal vasculature is a prominent factor in age-related macular degeneration. While many of the growth factors involved in this vascular remodeling are known, their regulation remains much less so. The hypothesis of the present study was that stimulation of human choroidal endothelial cells with the beta-adrenergic receptor agonist isoproterenol would lead to an increase in pigment epithelial derived factor (PEDF) and angiopoietin 1 (Ang1), markers of a stable vasculature. Protein levels of PEDF and Ang1 were significantly increased following stimulation with isoproterenol. However, isoproterenol also significantly increased protein levels of vascular endothelial cell growth factor, which is active during vasculature remodeling. These data suggest that beta-adrenergic receptor agonists are likely upstream of a number of growth factors implicated in ocular disease and have multiple effects on choroidal endothelial cells. Modulation of this signaling in the choroid may offer a new avenue for therapeutics.
Steinle
Jena J
JJ
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA. jjsteinle@utmem.edu
Cappocia
Frank C
FC
Jiang
Youde
Y
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D042683:Angiopoietin-1 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002829:Choroid / Q000166:cytology / Q000378:metabolism*; D020256:Choroidal Neovascularization; D042783:Endothelial Cells / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
D000318:Adrenergic beta-Agonists; D042683:Angiopoietin-1; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol; D009414:Nerve Growth Factors; D011943:Receptors, Adrenergic, beta; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor