Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes

Cardiac hypertrophy is a compensatory response to increased work load or stress on the heart, but over time can lead to heart failure and death. The molecular mechanisms underlying this disease are still not completely understood, however the Rho/Rho kinase pathway has been shown to play a role. N-[...

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Main Author: Moreau, Steven
Language:en
Published: 2012
Subjects:
Online Access:http://hdl.handle.net/10393/22887
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spelling ndltd-LACETR-oai-collectionscanada.gc.ca-OOU.#10393-228872013-10-04T04:23:44ZCharacterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied CardiomyocytesMoreau, Stevencardiac hypertrophyrho kinasepositron emission tomographyN-[11C]-methyl-hydroxyfasudilCardiac hypertrophy is a compensatory response to increased work load or stress on the heart, but over time can lead to heart failure and death. The molecular mechanisms underlying this disease are still not completely understood, however the Rho/Rho kinase pathway has been shown to play a role. N-[11C]-methyl-hydroxyfasudil, a PET radiotracer, binds to active Rho kinase and could be a possible tracer for hypertrophy. Hypertrophy was induced in vitro using the β-adrenergic receptor agonist isoproterenol to evaluate optimal Rho kinase activity. Rho kinase activity data was correlated to N-[11C]-methyl-hydroxyfasudil binding. Cardiac hypertrophy was verified with an increase in nuclear size (1.74 fold) and cell size (~2 fold), activation of hypertrophic signalling pathways, and increased Rho kinase activity (1.64 fold). This correlated to a 10.3% increase in N-[11C]-methyl-hydroxyfasudil binding. This data suggests that N-[11C]-methyl-hydroxyfasudil may be useful as a radiotracer for detecting cardiac hypertrophy and merits further in vivo investigation.2012-06-06T09:18:23Z2012-06-06T09:18:23Z20122012-06-06Thèse / Thesishttp://hdl.handle.net/10393/22887en
collection NDLTD
language en
sources NDLTD
topic cardiac hypertrophy
rho kinase
positron emission tomography
N-[11C]-methyl-hydroxyfasudil
spellingShingle cardiac hypertrophy
rho kinase
positron emission tomography
N-[11C]-methyl-hydroxyfasudil
Moreau, Steven
Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
description Cardiac hypertrophy is a compensatory response to increased work load or stress on the heart, but over time can lead to heart failure and death. The molecular mechanisms underlying this disease are still not completely understood, however the Rho/Rho kinase pathway has been shown to play a role. N-[11C]-methyl-hydroxyfasudil, a PET radiotracer, binds to active Rho kinase and could be a possible tracer for hypertrophy. Hypertrophy was induced in vitro using the β-adrenergic receptor agonist isoproterenol to evaluate optimal Rho kinase activity. Rho kinase activity data was correlated to N-[11C]-methyl-hydroxyfasudil binding. Cardiac hypertrophy was verified with an increase in nuclear size (1.74 fold) and cell size (~2 fold), activation of hypertrophic signalling pathways, and increased Rho kinase activity (1.64 fold). This correlated to a 10.3% increase in N-[11C]-methyl-hydroxyfasudil binding. This data suggests that N-[11C]-methyl-hydroxyfasudil may be useful as a radiotracer for detecting cardiac hypertrophy and merits further in vivo investigation.
author Moreau, Steven
author_facet Moreau, Steven
author_sort Moreau, Steven
title Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
title_short Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
title_full Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
title_fullStr Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
title_full_unstemmed Characterizing Rho Kinase Activity Using a Novel PET Tracer in Hypertrophied Cardiomyocytes
title_sort characterizing rho kinase activity using a novel pet tracer in hypertrophied cardiomyocytes
publishDate 2012
url http://hdl.handle.net/10393/22887
work_keys_str_mv AT moreausteven characterizingrhokinaseactivityusinganovelpettracerinhypertrophiedcardiomyocytes
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