TY - JOUR
T1 - A MALDI Mass Spectrometry Imaging Sample Preparation Method for Venous Thrombosis with Initial Lipid Characterization of Lab-Made and Murine Clots
AU - McDonald, Riley G.
AU - Poulos, Demitria A.
AU - Woodall, Brittni
AU - Gutzwiller, Leah
AU - Sheth, Rahul A.
AU - Good, Bryan C.
AU - Crouch, Anna Colleen
N1 - Funding Information:
The authors would like to thank the Biological and Small Molecule Mass Spectrometry Core (BSMMSC) for their contribution to the LC-MS analysis and for time on the MALDI-MS.
Publisher Copyright:
© 2023 American Society for Mass Spectrometry. Published by American Chemical Society. All rights reserved.
PY - 2023/9/6
Y1 - 2023/9/6
N2 - Venous thromboembolism (VTE) and its complications affect over 900,000 people in the U.S. annually, with a third of cases resulting in fatality. Despite such a high incidence rate, venous thrombosis research has not led to significant changes in clinical treatments, with standard anti-coagulant therapy (heparin followed by a vitamin K antagonist) being used since the 1950s. Mechanical thrombectomy is an alternative strategy for treating venous thrombosis; however, clinical guidelines for patient selection have not been well-established or accepted. The effectiveness of both treatments is impacted by the heterogeneity of the thrombus, including the mechanical properties of its cellular components and its molecular makeup. A full understanding of the complex interplay between disease initiation and progression, biochemical molecular changes, tissue function, and mechanical properties calls for a multiplex and multiscale approach. In this work, we establish a protocol for using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to characterize spatial heterogeneity of biomolecules in lab-made blood clots and ex vivo murine thrombi. In this work, we compared (1) tissue preservation and cryosectioning methods, (2) various matrixes, 9-aminoacridine hydrochloride monohydrate (9AA), 2,5-dihydroxybenzoic acid (DHB), and alpha-cyano-4-hydroxycinnamic acid matrix (CHCA), (3) plasma-rich versus red-blood-cell rich lab-made blood clots, and (4) lab-made blood clots versus ex vivo murine thrombi. This project is the first step in our work to combine mass spectrometry imaging with biomechanical testing of blood clots to improve our understanding of VTE.
AB - Venous thromboembolism (VTE) and its complications affect over 900,000 people in the U.S. annually, with a third of cases resulting in fatality. Despite such a high incidence rate, venous thrombosis research has not led to significant changes in clinical treatments, with standard anti-coagulant therapy (heparin followed by a vitamin K antagonist) being used since the 1950s. Mechanical thrombectomy is an alternative strategy for treating venous thrombosis; however, clinical guidelines for patient selection have not been well-established or accepted. The effectiveness of both treatments is impacted by the heterogeneity of the thrombus, including the mechanical properties of its cellular components and its molecular makeup. A full understanding of the complex interplay between disease initiation and progression, biochemical molecular changes, tissue function, and mechanical properties calls for a multiplex and multiscale approach. In this work, we establish a protocol for using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to characterize spatial heterogeneity of biomolecules in lab-made blood clots and ex vivo murine thrombi. In this work, we compared (1) tissue preservation and cryosectioning methods, (2) various matrixes, 9-aminoacridine hydrochloride monohydrate (9AA), 2,5-dihydroxybenzoic acid (DHB), and alpha-cyano-4-hydroxycinnamic acid matrix (CHCA), (3) plasma-rich versus red-blood-cell rich lab-made blood clots, and (4) lab-made blood clots versus ex vivo murine thrombi. This project is the first step in our work to combine mass spectrometry imaging with biomechanical testing of blood clots to improve our understanding of VTE.
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U2 - 10.1021/jasms.3c00079
DO - 10.1021/jasms.3c00079
M3 - Article
C2 - 37439461
AN - SCOPUS:85165708769
SN - 1044-0305
VL - 34
SP - 1879
EP - 1889
JO - Journal of the American Society for Mass Spectrometry
JF - Journal of the American Society for Mass Spectrometry
IS - 9
ER -