Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance.
BACKGROUND
Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear.


RESULTS
Arterial injury was induced in wild-type (wt), leptin-deficient (lep(ob/ob)), and leptin receptor-deficient (lepr(db/db)) mice. Compared with wt mice, lep(ob/ob) and lepr(db/db) mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and lepr(db/db) mice indicated that the vascular protection in lepr(db/db) mice was not attributable to lack of leptin receptor expression on bone marrow-derived elements. To investigate the role of the lepr-mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, lepr(s/s) mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in lepr(s/s) mice was significantly increased compared with lepr(db/db) mice.


CONCLUSIONS
The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.
Bodary
Peter F
PF
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
Shen
Yuechun
Y
Ohman
Miina
M
Bahrou
Kristina L
KL
Vargas
Fernando B
FB
Cudney
Sarah S
SS
Wickenheiser
Kevin J
KJ
Myers
Martin G
MG
Eitzman
Daniel T
DT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology*; D005263:Femoral Artery / Q000293:injuries / Q000503:physiopathology; D020738:Leptin / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C515447:leptin receptor, mouse