Abstract
Abstract 9: Apelin Protects Against Arterial Thrombosis in Mice with Diet-induced Obesity
Arteriosclerosis, thrombosis, and vascular biology, Vol.33(suppl_1)
05/2013
DOI: 10.1161/atvb.33.suppl_1.A9
Abstract
Background and Hypothesis
The prevalence of obesity and related thrombotic diseases is increasing steadily, but the underlying mechanisms of thrombosis are not well elucidated. Apelin is a peptide adipokine that is upregulated in obesity and has protective effects on cardiovascular function. We tested the hypothesis that apelin protects from thrombosis in a mouse model of diet-induced obesity.
Methods
To induce obesity, male apelin null (
Apln -/y
) mice and wild-type (WT) littermates were fed a high fat (HF) diet with 60% of Kcal from fat (TD.06414) for 12 weeks. Susceptibility to thrombosis of the carotid artery was assessed using a photochemical injury (rose bengal) method. Expression of plasminogen activator inhibitor-1 (PAI-1) was measured by ELISA and real-time PCR.
Results
Body weight and fasting glucose were higher in mice fed the HF diet than in mice fed a control diet (P<0.05) but did not differ between
Apln -/y
and WT mice (P>0.05). The time to stable occlusion of the carotid artery was significantly accelerated in
Apln -/y
mice compared with WT mice (24.8±1.5 vs 43.9±6.8 min, P=0.04) fed the HF diet, but not a control diet. Because apelin is known to regulate the expression of the antifibrinolytic serpin PAI-1, we investigated the role of PAI-1 in the antithrombotic mechanism of apelin. Plasma levels of total PAI-1 were elevated 3-fold in WT mice fed the HF diet (P<0.05 vs. control diet). An even larger 5-fold elevation of plasma PAI-1 was seen in
Apln -/y
mice fed the HF diet (P<0.05). Levels of PAI-1 mRNA in lung also were significantly elevated in
Apln -/y
mice (P<0.01 vs. WT mice). To directly determine the role of PAI-1 in the prothrombotic phenotype of
Apln -/y
mice, a PAI-1-blocking antibody was administered prior to inducing thrombosis of the carotid artery. The PAI-1 antibody nearly completely reversed the shortened time to stable occlusion (P=0.03) in obese
Apln -/y
mice.
Conclusions
Endogenous apelin protects from arterial thrombosis in obesity, in part by dampening obesity-induced upregulation of PAI-1. These findings may have pharmacological implications for the prevention of thrombotic complications of obesity and metabolic syndrome.
Details
- Title: Subtitle
- Abstract 9: Apelin Protects Against Arterial Thrombosis in Mice with Diet-induced Obesity
- Creators
- Hong Jin - University of IowaKatina M Wilson - University of IowaAnil K Chauhan - University of IowaPhilip S Tsao - Stanford UniversitySteven R Lentz - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.33(suppl_1)
- DOI
- 10.1161/atvb.33.suppl_1.A9
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984361724702771
Metrics
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