Plasminogen activator inhibitor-1 contributes to the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice.
BACKGROUND
It is widely accepted that obesity is a risk factor for ischemic heart disease, but the association with stroke is less clear. Adipose tissue is an important source of plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of plasminogen activation.


OBJECTIVE
To test the hypothesis that elevated PAI-1 levels associated with obesity negatively affect the outcome of thrombotic ischemic stroke.


METHODS
Middle cerebral artery (MCA) occlusion was induced photochemically in mice with nutritionally induced or genetically determined obesity and their lean counterparts.


RESULTS
The MCA occlusion time (to obtain complete occlusion) was significantly shorter in obese (nutritionally induced) than in lean wild-type (WT) C57Bl/6 mice, whereas the infarct size was significantly larger and intracranial hemorrhage (ICH) was enhanced (all P < 0.05). Similar observations were made in genetically obese ob/ob mice, as compared to lean WT littermates. In both strains, obesity was associated with markedly elevated circulating PAI-1 levels, probably originating from the fat tissue. In contrast, PAI-1-deficient lean and obese mice did not display significant differences in MCA occlusion time, infarct volume or ICH.


CONCLUSIONS
Plasminogen activator inhibitor-1 may play a functional role in the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice.
Nagai
N
N
Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
Van Hoef
B
B
Lijnen
H R
HR
D000818:Animals; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy; D007511:Ischemia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications*; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D020521:Stroke / Q000628:therapy*; D013927:Thrombosis / Q000473:pathology* / Q000628:therapy; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome
D017395:Plasminogen Activator Inhibitor 1