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Oscillatory shear stress induces hemostatic imbalance in healthy men.

Thrombosis research (2018-09-03)
Amanda Sampaio Storch, Helena Naly Miguens Rocha, Vinicius Pacheco Garcia, Gabriel Matheus da Silva Batista, João Dario Mattos, Monique Opuszcka Campos, André Lopes Fuly, Antonio Claudio Lucas da Nóbrega, Igor Alexandre Fernandes, Natália Galito Rocha
ABSTRACT

In vitro and animal model studies have demonstrated that oscillatory shear can trigger vascular hemostasis and remodeling. However, the roles of hemodynamic forces in vascular human biology are not well understood. This study aimed to determine the effects of increasing oscillatory shear stress (OSS) on coagulation/fibrinolysis factors and matrix metalloproteinase-9 activity in healthy subjects. Ten healthy males (35 ± 7 years) underwent a 30-minute dominant forearm cuff occlusion (75 mm Hg) to exacerbate OSS in the brachial artery. Blood flow was quantified (Doppler ultrasound), and plasma samples were obtained from both arms at rest and during the last 30 s of cuff occlusion on the dominant arm. A proximal cuff (40 mm Hg, close to axilla) was also occluded to facilitate venous blood biomarker trapping. The retrograde shear rate and oscillatory shear index were increased and the mean shear rate, mean blood velocity, and mean blood flow were decreased in the cuffed arm (p < 0.05 vs. baseline and non-cuffed arm). Cuff occlusion induced increases in platelet microparticle release (p = 0.05 vs. baseline), prothrombin time (p < 0.05 vs. baseline and non-cuffed arm), tissue plasminogen activator (p < 0.01 vs. baseline and non-cuffed arm), plasminogen activator inhibitor-1 (p < 0.02 vs. baseline and non-cuffed arm), and matrix metalloproteinase-9 activity (p = 0.01 vs. baseline). No significant changes were found in the non-cuffed arm throughout the protocol. Exacerbation of OSS induced in vivo disturbances in platelet microparticle release, coagulation-fibrinolysis, and matrix metalloproteinase-9 activity in healthy individuals. These are potential mechanisms involved in OSS-mediated endothelial dysfunction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Human PLG (Plasminogen) ELISA Kit, for cell culture supernatants, plasma, and serum samples
Sigma-Aldrich
(±)-2-(p-Methoxyphenoxy)propionic acid, ≥98%
Sigma-Aldrich
Picropodophyllotoxin, ≥96% (HPLC), powder