Adiponectin acts as an endogenous antithrombotic factor.
OBJECTIVE
Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive.


RESULTS
We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36+/-4.25 x 10(7) arbitrary units for APN-KO and 6.74+/-2.87x10(7) arbitrary units for WT; n=10; P<0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s(-1), as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation.


CONCLUSIONS
Adiponectin deficiency leads to enhanced thrombus formation and platelet aggregation. The present study reveals a new role of adiponectin as an endogenous antithrombotic factor.
Kato
Hisashi
H
Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Japan.
Kashiwagi
Hirokazu
H
Shiraga
Masamichi
M
Tadokoro
Seiji
S
Kamae
Tsuyoshi
T
Ujiie
Hidetoshi
H
Honda
Shigenori
S
Miyata
Shigeki
S
Ijiri
Yoshinobu
Y
Yamamoto
Junichiro
J
Maeda
Norikazu
N
Funahashi
Tohru
T
Kurata
Yoshiyuki
Y
Shimomura
Iichiro
I
Tomiyama
Yoshiaki
Y
Kanakura
Yuzuru
Y
D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000502:physiology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism*; D003094:Collagen; D039421:Integrin alpha2 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology*; D010976:Platelet Count; D011673:Pulsatile Flow; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism*
D052242:Adiponectin; D039421:Integrin alpha2; D039661:Integrin beta3; D019007:P-Selectin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D003094:Collagen