Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats.
The metabolic syndrome in association with obesity is a major clinical problem inducing hypertension, diabetes mellitus, and atherosclerosis. Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. We evaluated the growth of ECs and intracellular signalings in response to leptin in vitro and the angiogenic effects of leptin in the cornea in vivo with and without adenovirus-mediated transfer of the OB-Rb gene in Zucker fatty (ZF) rats as a model for the metabolic syndrome. Recombinant adenovirus vector encoding rat OB-Rb (Ad.OB-Rb) or Escherichia coli. LacZ (Ad.LacZ) was transfected into cultured ECs from Zucker lean (ZL) rats and ZF rats. Leptin increased DNA synthesis dose-dependently in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb, but not with Ad.LacZ, improved the growth effects of leptin in ECs from ZF rats. Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. Leptin induced angiogenesis in cornea from ZL rats, but not from ZF rats. Coadministration of leptin and Ad.OB-Rb induced angiogenesis in cornea from ZF rats. Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome.
Jin
Xueqing
X
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Fukuda
Noboru
N
Su
Jinzi
J
Takagi
Hiroto
H
Lai
Yimu
Y
Lin
Zhihong
Z
Kanmatsuse
Katsuo
K
Wang
Zhuo-Wei
ZW
Unger
Roger H
RH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D016510:Corneal Neovascularization / Q000139:chemically induced; D004247:DNA / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D020738:Leptin / Q000494:pharmacology*; D009765:Obesity / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D001616:beta-Galactosidase / Q000494:pharmacology
D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D004247:DNA; D001616:beta-Galactosidase