Zengsheng Chen1, Nandan K Mondal1, Jun Ding2, Jingya Gao3, Bartley P Griffith1, Zhongjun J Wu4. 1. Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 2. Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Mechanical Engineering, University of Maryland, Baltimore County, Baltimore, MD 21250, USA. 3. Department of Chemistry and Biochemistry, School of Science, Siena College, Loudonville, NY 12211, USA. 4. Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: zhongjun.wu@louisville.edu.
Abstract
INTRODUCTION: The structural integrity of platelet receptors is essential for platelets to function normally in hemostasis and thrombosis in response to physiological and pathological stimuli. The aim of this study was to examine the shedding of two key platelet receptors, glycoprotein (GP) Ibα and GPVI, after exposed to the non-physiological high shear stress environment which commonly exists in blood contacting medical devices and stenotic blood vessels. MATERIALS AND METHODS: In this in vitro experiment, we exposed healthy donor blood in our specially designed blood shearing device to three high shear stress levels (150, 225, 300 Pa) in combination with two short exposure time conditions (0.05 and 0.5 sec.). The expression and shedding of platelet GPIbα and GPVI receptors in the sheared blood samples were characterized using flow cytometry. The ability of platelet aggregation induced by ristocetin and collagen related to GPIbα and GPVI in the sheared blood samples, respectively, was evaluated by aggregometry. RESULTS AND CONCLUSIONS: Compared to the normal blood, the surface expression of platelet GPIbα and GPVI in the sheared blood significantly decreased with increasing shear stress and exposure time. Moreover, the platelet aggregation induced by ristocetin and collagen reduced remarkably in a similar fashion. In summary non-physiological high shear stresses with short exposure time can induce shedding of platelet GPIbα and GPVI receptors, which may lead platelet dysfunction and influence the coagulation system. This study may provide a mechanistic insight into the platelet dysfunction and associated bleeding complication in patients supported by certain blood contacting medical devices.
INTRODUCTION: The structural integrity of platelet receptors is essential for platelets to function normally in hemostasis and thrombosis in response to physiological and pathological stimuli. The aim of this study was to examine the shedding of two key platelet receptors, glycoprotein (GP) Ibα and GPVI, after exposed to the non-physiological high shear stress environment which commonly exists in blood contacting medical devices and stenotic blood vessels. MATERIALS AND METHODS: In this in vitro experiment, we exposed healthy donor blood in our specially designed blood shearing device to three high shear stress levels (150, 225, 300 Pa) in combination with two short exposure time conditions (0.05 and 0.5 sec.). The expression and shedding of platelet GPIbα and GPVI receptors in the sheared blood samples were characterized using flow cytometry. The ability of platelet aggregation induced by ristocetin and collagen related to GPIbα and GPVI in the sheared blood samples, respectively, was evaluated by aggregometry. RESULTS AND CONCLUSIONS: Compared to the normal blood, the surface expression of platelet GPIbα and GPVI in the sheared blood significantly decreased with increasing shear stress and exposure time. Moreover, the platelet aggregation induced by ristocetin and collagen reduced remarkably in a similar fashion. In summary non-physiological high shear stresses with short exposure time can induce shedding of platelet GPIbα and GPVI receptors, which may lead platelet dysfunction and influence the coagulation system. This study may provide a mechanistic insight into the platelet dysfunction and associated bleeding complication in patients supported by certain blood contacting medical devices.
Authors: Xinwei Song; Alexandrina Untaroiu; Houston G Wood; Paul E Allaire; Amy L Throckmorton; Steven W Day; Donald B Olsen Journal: ASAIO J Date: 2004 May-Jun Impact factor: 2.872
Authors: Warwick S Nesbitt; Suhasini Kulkarni; Simon Giuliano; Isaac Goncalves; Sacha M Dopheide; Cindy L Yap; Ian S Harper; Hatem H Salem; Shaun P Jackson Journal: J Biol Chem Date: 2001-11-16 Impact factor: 5.157
Authors: V Kasirajan; P M McCarthy; K J Hoercher; R C Starling; J B Young; M K Banbury; N G Smedira Journal: Semin Thorac Cardiovasc Surg Date: 2000-07
Authors: Warwick S Nesbitt; Simon Giuliano; Suhasini Kulkarni; Sacha M Dopheide; Ian S Harper; Shaun P Jackson Journal: J Cell Biol Date: 2003-03-31 Impact factor: 10.539
Authors: B Nieswandt; V Schulte; W Bergmeier; R Mokhtari-Nejad; K Rackebrandt; J P Cazenave; P Ohlmann; C Gachet; H Zirngibl Journal: J Exp Med Date: 2001-02-19 Impact factor: 14.307
Authors: Zengsheng Chen; Nandan K Mondal; Shirong Zheng; Steven C Koenig; Mark S Slaughter; Bartley P Griffith; Zhongjun J Wu Journal: Platelets Date: 2017-11-28 Impact factor: 3.862
Authors: Nandan K Mondal; Zengsheng Chen; Jaimin R Trivedi; Erik N Sorensen; Si M Pham; Mark S Slaughter; Bartley P Griffith; Zhongjun J Wu Journal: ASAIO J Date: 2018 Jul/Aug Impact factor: 2.872
Authors: Nandan K Mondal; Tieluo Li; Zengsheng Chen; Hegang H Chen; Erik N Sorensen; Si M Pham; Michael A Sobieski; Steven C Koenig; Mark S Slaughter; Bartley P Griffith; Zhongjun J Wu Journal: Mol Cell Biochem Date: 2017-03-25 Impact factor: 3.396
Authors: Nesreen Z Alsmadi; Sarah J Shapiro; Christopher S Lewis; Vinit M Sheth; Trevor A Snyder; David W Schmidtke Journal: Biomicrofluidics Date: 2017-11-28 Impact factor: 2.800
Authors: Nandan K Mondal; Zengsheng Chen; Jaimin R Trivedi; Erik N Sorensen; Si M Pham; Mark S Slaughter; Bartley P Griffith; Zhongjun J Wu Journal: Thromb Res Date: 2017-09-08 Impact factor: 3.944
Authors: Yana Roka-Moiia; Samuel Miller-Gutierrez; Daniel E Palomares; Joseph E Italiano; Jawaad Sheriff; Danny Bluestein; Marvin J Slepian Journal: Arterioscler Thromb Vasc Biol Date: 2021-02-11 Impact factor: 8.311