Leptin inhibits cell growth of human vascular smooth muscle cells.
Elevated leptin levels are thought to contribute to the individual cardiovascular risk, however, the role of leptin in the pathogenesis of atherosclerosis remains unclear. The aim of our study was to elucidate the effects of leptin on growth of human vascular smooth muscle cells (VSMC) and leptin receptor expression. By establishing a new quantitative real-time PCR for leptin receptor (ObR) isoforms we showed that the short isoforms of ObR were expressed in a 10- to 27-fold excess compared to the long isoform in cultured human VSMCs. Incubation of VSMCs with 100 ng/ml leptin downregulated the short isoforms significantly, whereas the long isoform was not influenced. Increasing leptin concentrations of 50 and 100 ng/ml significantly reduced the cell number of VSMCs compared to untreated controls. Our findings suggest a role for leptin in vascular smooth muscle cell growth, associated to a downregulation of leptin receptor isoforms.
Bohlen
Felix
F
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital, Paul-List-Str 13-15, 04103 Leipzig, Germany.
Kratzsch
Juergen
J
Mueller
Marc
M
Seidel
Bert
B
Friedman-Einat
Miriam
M
Witzigmann
Helmut
H
Teupser
Daniel
D
Koerner
Antje
A
Storck
Martin
M
Thiery
Joachim
J
D000368:Aged; D001011:Aorta / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007083:Iliac Artery / Q000187:drug effects; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D054411:Receptors, Leptin
D006131:Growth Inhibitors; C515448:LEPR protein, human; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin