Send to

Choose Destination
See comment in PubMed Commons below
Diabetes. 2012 Dec;61(12):3219-27. doi: 10.2337/db12-0162. Epub 2012 Aug 13.

Obesity-induced endothelial dysfunction is prevented by deficiency of P-selectin glycoprotein ligand-1.

Author information

Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, Michigan, USA.


Endothelial dysfunction precedes atherosclerosis and represents an important link between obesity and cardiovascular events. Strategies designed to prevent endothelial dysfunction may therefore reduce the cardiovascular complications triggered by obesity. We tested the hypothesis that deficiency of P-selectin glycoprotein ligand-1 (Psgl-1) would improve the endothelial dysfunction associated with obesity. Psgl-1-deficient (Psgl-1(-/-)) and wild-type (Psgl-1(+/+)) mice were fed standard chow or a high-fat, high-sucrose diet (diet-induced obesity [DIO]) for 10 weeks. DIO increased mesenteric perivascular adipose tissue (mPVAT) macrophage content and vascular oxidative stress in Psgl-1(+/+) mice but not in Psgl-1(-/-) mice. Pressure myography using mesenteric arteries demonstrated that relaxation responses to acetylcholine were significantly impaired in DIO Psgl-1(+/+) mice, whereas DIO Psgl-1(-/-) mice were protected from endothelial dysfunction with similar relaxation responses to Psgl-1(+/+) or Psgl-1(-/-) mice fed standard chow. The superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) partially recovered impaired endothelial function induced by DIO. A neutralizing Psgl-1 antibody was also effective in preventing endothelial dysfunction and reducing mPVAT macrophage content induced by DIO. These results indicate that obesity in mice leads to PVAT inflammation and endothelial dysfunction that is prevented by Psgl-1 deficiency. Psgl-1 inhibition may be a useful treatment strategy for targeting vascular disease associated with obesity.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center