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Platelet Mechanobiology - Shear, Membranes, Fluidity and Stiffness! Opportunities for Novel Biochemical Strategies to Improve Cardiovascular Health

Sep
30
3:30 pm to 4:30 pm
Chemistry and Biochemistry Department Logo

I will present new mechanisms and the latest understanding of platelet activation. Cardiovascular therapeutic devices (CTDs) – e.g. ventricular assist devices, total artificial heart, percutaneous heart valves, and stents – are life-saving therapeutics increasingly utilized worldwide. Despite CTD efficacy they remain plagued by thrombosis, leading to device malfunction, embolic events, and death. Central in CTD thrombosis is platelet activation due to supraphysiologic shear stress exposure (hypershear), often > 1000 dynes/cm2, associated with turbulent flows through these devices, particularly in the “free flow” (non-wall contacting) regions; this activation is independent of widely studied GPIb-von Willebrand factor activation-adhesive biochemical mechanisms. We have established that current clinical antiplatelet agents, targeting biochemical agonists and pathways, have little to no efficacy in limiting Shear-Mediated Platelet Activation (SMPA) in CTDs, which poses a significant barrier to their therapeutic use. I will address this gap in CTD therapy by defining SMPA mechanisms and identifying candidate agents as a means of limiting SMPA and CTD thrombosis. Studies from our lab indicate that cell-mechanobiological mechanisms are the predominant driver in SMPA, and that modulating platelet biomechanical properties, e.g. membrane fluidity and cell stiffness, via the addition of Exogenous Lipophilic Molecules (ELMs), is a promising means of limiting SMPA. As such a central hypothesis of our research group is that platelet biomechanical properties are key determinants of SMPA, and modulation of these properties will block SMPA. As an outgrowth of our work representative agents of an expanding novel class of therapeutic compounds which we have termed “mechanoceuticals’ will be discussed. Studies with these and related agents related to membrane fluidity, cell stiffness and limitation of microparticle generation will be addressed. The ultimate goal and translational path of this work is to identify clinically useful mechanoceutical agents that will reduce thrombosis in CTDs, leading to reduced patient mortality rates an improved quality of life.

Zoom passcode: UACBC

Marvin Slepian, MD
Marvin Slepian, MD
Regents Professor of Medicine – Cardiology
Department of Biomedical Engineering, University of Arizona

Professor of Medical Imaging
Professor and Associate Department Head - BioMedical Engineering
Professor of Materials Sciences and Engineering
Professor of Chemical and Environmental Engineering
McGuire Scholar, Eller College of Management
Director, ACABI – Arizona Center for Accelerated BioMedical Innovation
University of Arizona
President - ASAIO American Society for Artificial Internal Organs

To request any disability-related accommodations for this event please contact the event coordinator at least three business days prior to the event.
Sep
30
3:30 pm to 4:30 pm
Thursday, September 30, 2021 - 3:30pm

AUDIENCE

Faculty, Staff, Students, Alumni, Community
College of Medicine – Tucson
College of Pharmacy

LOCATION

Tucson area
Virtual
Main Campus – Tucson
Henry Koffler Building
Room 218
1340 E University Blvd, Tucson AZ 85721

CONTACT

Ellie Warder
College of Medicine – Tucson
Chemistry and Biochemistry