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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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 |
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en |
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cardiac hypertrophy rho kinase positron emission tomography N-[11C]-methyl-hydroxyfasudil |
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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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1716603848978595840 |