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Effects of Nanomaterials on Human Blood Coagulation

EPA Grant Number: R832843
Title: Effects of Nanomaterials on Human Blood Coagulation
Investigators: Perrotta, Peter L. , Gouma, Pelagia-Irene
Institution: West Virginia University
EPA Project Officer: Lasat, Mitch
Project Period: February 1, 2006 through January 31, 2009
Project Amount: $375,000
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: A Joint Research Solicitation - EPA, NSF, NIOSH (2005)
Research Category: Nanotechnology , Health Effects

Description:

Objective:

The goal of this project is to determine the effects of commercially available nanomaterials on the human blood coagulation system. The rationale is based on the fact that common human diseases, such as myocardial infarction, are caused by abnormalities of blood coagulation that predispose to thrombosis (clots) and these diseases are clearly influenced by environmental factors. Because of their large surface area and reactivity, nanomaterials that enter the workplace or home have the potential to adversely affect blood coagulation, which could result in clotting abnormalities.

Approach:

A comprehensive approach will be used to study how a wide-range of commercially prepared nanomaterials affects human blood coagulation. Techniques will focus on the two major components of the clotting system: blood coagulation proteins and platelets. First, the toxic effects of nanomaterials on blood clotting proteins will be studied using coagulation-specific laboratory assays. We will focus on the ability of nanomaterials to promote and/or retard the catalytic activity of coagulation enzymes. This is because adsorption of enzymes on the extensive available surface of nanomaterials may alter the functional groups of the enzymes and, hence, their enzymatic activity. Surface interactions between blood coagulation proteins and nanomaterials will be further detailed at the molecular level using surface plasmon resonance and atomic force microscopy. Finally, classes of nanomaterials will be identified that have the ability to “activate” human platelets because platelet activation plays a role in many thrombotic diseases.

Expected Results:

Studies outlined in this proposal will identify nanomaterials that can harm the human blood coagulation system. Furthermore, thresholds of toxicity and dose-response effects of coagulation proteins to nanomaterials will be quantified. The advanced techniques utilized will help to understand the complex interactions between nanomaterials, coagulation enzymes, and platelets. Through our findings a system for classifying engineered nanomaterials based on their physiologic effects on blood coagulation will be developed. This will help to predict whether novel classes of nanomaterials and/or functionalized nanomaterials can potentially harm human blood coagulation.

Supplemental Keywords:

nanotechnology, environmental factors, thrombosis, biology, engineering, pathology, adsorption, chemical transport, risk assessment, health effects, human health, dose response, enzymes, cumulative effects, chemicals, toxics, particulates, analytical, , ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, Risk Assessment, Risk Assessments, Health Risk Assessment, Biochemistry, Environmental Microbiology, bioavailability, exposure assessment, nanotechnology, analysis of chemical exposure, blood clotting, blood coagulation enzymes, nanomaterials

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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