Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding

Mengchen Yang; Katie L. Houck; Xinlong Dong; Maria Hernandez; Yi Wang; Sriram S. Nathan; Xiaoping Wu; Vahid Afshar-Kharghan; Xiaoyun Fu; Miguel A. Cruz; Jianning Zhang; Angelo Nascimbene; Jing fei Dong

doi:10.1016/j.jacbts.2021.12.005

Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding

Mengchen Yang, Katie L. Houck, Xinlong Dong, Maria Hernandez, Yi Wang, Sriram S. Nathan, Xiaoping Wu, Vahid Afshar-Kharghan, Xiaoyun Fu, Miguel A. Cruz, Jianning Zhang, Angelo Nascimbene, Jing fei Dong

Pulmonary Medicine

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner. Our findings suggest that LVAD-driven high shear stress primarily activates VWF, rather than inducing cleavage in the majority of patients.

Original language	English (US)
Pages (from-to)	247-261
Number of pages	15
Journal	JACC: Basic to Translational Science
Volume	7
Issue number	3P1
DOIs	https://doi.org/10.1016/j.jacbts.2021.12.005
State	Published - Mar 2022

Keywords

angiogenesis
extracellular vesicles
left ventricular assist devices
platelets
shear stress
von Willebrand factor

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2021.12.005

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Yang, M., Houck, K. L., Dong, X., Hernandez, M., Wang, Y., Nathan, S. S., Wu, X., Afshar-Kharghan, V., Fu, X., Cruz, M. A., Zhang, J., Nascimbene, A., & Dong, J. F. (2022). Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding. JACC: Basic to Translational Science, 7(3P1), 247-261. https://doi.org/10.1016/j.jacbts.2021.12.005

Yang, M, Houck, KL, Dong, X, Hernandez, M, Wang, Y, Nathan, SS, Wu, X, Afshar-Kharghan, V, Fu, X, Cruz, MA, Zhang, J, Nascimbene, A & Dong, JF 2022, 'Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding', JACC: Basic to Translational Science, vol. 7, no. 3P1, pp. 247-261. https://doi.org/10.1016/j.jacbts.2021.12.005

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title = "Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding",

abstract = "Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner. Our findings suggest that LVAD-driven high shear stress primarily activates VWF, rather than inducing cleavage in the majority of patients.",

keywords = "angiogenesis, extracellular vesicles, left ventricular assist devices, platelets, shear stress, von Willebrand factor",

author = "Mengchen Yang and Houck, {Katie L.} and Xinlong Dong and Maria Hernandez and Yi Wang and Nathan, {Sriram S.} and Xiaoping Wu and Vahid Afshar-Kharghan and Xiaoyun Fu and Cruz, {Miguel A.} and Jianning Zhang and Angelo Nascimbene and Dong, {Jing fei}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = mar,

doi = "10.1016/j.jacbts.2021.12.005",

language = "English (US)",

volume = "7",

pages = "247--261",

journal = "JACC: Basic to Translational Science",

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T1 - Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis

T2 - Implication for LVAD-Induced Bleeding

AU - Yang, Mengchen

AU - Houck, Katie L.

AU - Dong, Xinlong

AU - Hernandez, Maria

AU - Wang, Yi

AU - Nathan, Sriram S.

AU - Wu, Xiaoping

AU - Afshar-Kharghan, Vahid

AU - Fu, Xiaoyun

AU - Cruz, Miguel A.

AU - Zhang, Jianning

AU - Nascimbene, Angelo

AU - Dong, Jing fei

PY - 2022/3

Y1 - 2022/3

N2 - Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner. Our findings suggest that LVAD-driven high shear stress primarily activates VWF, rather than inducing cleavage in the majority of patients.

AB - Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner. Our findings suggest that LVAD-driven high shear stress primarily activates VWF, rather than inducing cleavage in the majority of patients.

KW - angiogenesis

KW - extracellular vesicles

KW - left ventricular assist devices

KW - platelets

KW - shear stress

KW - von Willebrand factor

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JO - JACC: Basic to Translational Science

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Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding

Abstract

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