title: Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis.
abstract: Shear-mediated platelet activation (SMPA) is central in thrombosis of implantable cardiovascular therapeutic devices. Despite the morbidity and mortality associated with thrombosis of these devices, our understanding of mechanisms operative in SMPA, particularly in free flowing blood, remains limited. Herein we present and discuss a range of emerging mechanisms for consideration for "free flow" activation under supraphysiologic shear. Further definition and manipulation of these mechanisms will afford opportunities for novel pharmacologic and mechanical strategies to limit SMPA and enhance overall implant device safety.
authors.affiliation: Departments of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States; Department of Biomedical Engineering, Stony Brook University, NY 11794, United States. Electronic address: chairman.syns@gmail.com.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Slepian
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, NY 11794, United States.
authors.forename: Jawaad
authors.initials: J
authors.lastname: Sheriff
authors.affiliation: Departments of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Departments of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: Phat
authors.initials: P
authors.lastname: Tran
authors.affiliation: Departments of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: Naing
authors.initials: N
authors.lastname: Bajaj
authors.affiliation: Departments of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: Joe G N
authors.initials: JGN
authors.lastname: Garcia
authors.affiliation: Departments of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: S
authors.initials: S
authors.lastname: Scott Saavedra
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, NY 11794, United States.
authors.forename: Danny
authors.initials: D
authors.lastname: Bluestein
mesh_terms: D001792:Blood Platelets / Q000502:physiology; D006801:Humans; D015539:Platelet Activation; D019736:Prostheses and Implants / Q000009:adverse effects; D013314:Stress, Mechanical; D013927:Thrombosis / Q000503:physiopathology*
keywords: Fluid shear stress; Mechanical circulatory support; Mechanotransduction; Platelet activation; Thrombosis