Implication of free fatty acids in thrombin generation and fibrinolysis in vascular inflammation in Zucker rats and evolution with aging

Walton, LA ORCID: 0000-0002-8651-7443 2017, 'Implication of free fatty acids in thrombin generation and fibrinolysis in vascular inflammation in Zucker rats and evolution with aging' , Frontiers in Physiology, 8 (949) .

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Abstract

Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis.
Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS.
Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT).
Results: Endogenous thrombin potential (ETP) was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL)-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats.
Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

Item Type: Article
Schools: Schools > School of Health Sciences > Centre for Health Sciences Research
Journal or Publication Title: Frontiers in Physiology
Publisher: BMC
ISSN: 1664-042X
Related URLs:
Funders: Institut National de la Santé et de la Recherche Médical
Depositing User: LA Walton
Date Deposited: 22 Nov 2017 12:40
Last Modified: 16 Dec 2017 17:21
URI: http://usir.salford.ac.uk/id/eprint/44421

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