Leptin stimulates rat aortic smooth muscle cell proliferation and migration.
Leptin, a peptide secreted from adipose tissue, plays an important role in the regulation of food intake and energy expenditure. In obese patients, plasma leptin levels are elevated and obesity is one of the major risk factors for cardiovascular diseases. Therefore, in this study, we investigated the effect of leptin on vascular smooth muscle cell (VSMC) functions. Cultured rat aortic VSMC expressed 130-kDa short form of leptin receptor. Leptin stimulated both proliferation and migration of VSMC. Leptin stimulated phosphorylation and activation of mitogen-activated protein (MAP) kinases, and also increased phosphatidylinositol (PI) 3-kinase activity. Further, two distinct PI 3-kinase inhibitors, wortmannin and LY294002 inhibited the migratory effect of leptin. These results demonstrate that leptin is a proliferative and migratory factor for VSMC, implying that leptin may play a role in the formation and development of vascular lesions.
Oda
A
A
First Division, Department of Internal Medicine, Kobe University School of Medicine.
Taniguchi
T
T
Yokoyama
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D002352:Carrier Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000077191:Wortmannin
D000730:Androstadienes; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D020738:Leptin; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019000:Phosphotyrosine; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000077191:Wortmannin; C515448:LEPR protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one