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Leu33Pro (PlA) polymorphism of integrin beta3 modulates platelet Src pY418 and focal adhesion kinase pY397 phosphorylation in response to abnormally high shear stress

Huynh, Khona; Nguyen, Thi-Hiepa; Nguyen, Phuong Thaoa; Tran, Ngoc Quyenb,c; Vo, Van Toia; Gyenes, Mariannad; Stoldt, Volker R.d

Blood Coagulation & Fibrinolysis: September 2018 - Volume 29 - Issue 6 - p 488–495
doi: 10.1097/MBC.0000000000000744

Objectives Shear stress can activate platelet integrin-mediated signaling that leads to shear-induced platelet aggregation (SIPA) and eventually contribute to acute myocardial infarction. The major platelet integrin αIIbβ3 is polymorphic at residue 33 [Leu33Pro (PlA) polymorphism]. The Pro33 isoform has been shown to have a prothrombotic phenotype. In this work, we studied the impact of Leu33/Pro33 polymorphism on the shear-induced integrin-mediated Src and FAK activation in platelets.

Methods Platelets of both genotypes were placed on immobilized fibrinogen or heat activated BSA and were exposed to physiological (500/s) or abnormally high (5000/s) shear rates for 2–10 min. Platelets after exposure to shear were analysed for Src pY418 and FAK pY397 activities.

Results Whereas physiological shear stress does not affect platelet signaling, abnormally high-shear stress considerably elevates Src and FAK phosphorylation in both Pro33 and Leu33 platelets. Both under static and flow conditions, Pro33 platelets exhibited a significantly higher Src and FAK activities than Leu33 platelets. Interestingly, even in the absence of the αIIbβ3-fibrinogen interaction, we could detect a shear-induced integrin-mediated signaling of Src and FAK in platelets. In parallel experiments in which platelets were pretreated with abciximab, an integrin αIIbβ3 antagonist, activation of both kinases by shear was inhibited.

Conclusion Taken together, our data indicates an important role of αIIbβ3 and shows that Leu33Pro polymorphism modulates the integrin-mediated Src and FAK signaling in platelets in response to shear stress.

aBiomedical Engineering Department, International University, Vietnam National University

bGraduate School of Science and Technology Viet Nam, Vietnam Academy of Science and Technology

cInstitute of Applied Materials Science, Vietnam Academy of Science and Technology, Ho Chi Minh City, Vietnam

dDepartment of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

Correspondence to Khon Huynh, PhD, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City, Vietnam, Quarter 6, Linh Trung ward, Thu Duc district, Ho Chi Minh city, Vietnam. Tel: +84 8 37 24 42 70 x3296; fax: +84 8 37 24 42 71; e-mail:

Received 1 February, 2018

Revised 3 May, 2018

Accepted 6 June, 2018

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