Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII

The objective of this study was to establish whether 1) hyperactivity of renin-angiotensin-aldosterone system (RAAS) produces apoptosis in early stages of cardiac disease; and 2) Ca2+-calmodulin-dependent protein kinase II (CaMKII) is involved in these apoptotic events. Two models of hypertrophy wer...

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Autores principales: Vélez Rueda, Jorge Omar, Palomeque, Julieta, Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/106764
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3774203&blobtype=pdf
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id I19-R120-10915-106764
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
angiotensin II
Ca2+-calmodulin-dependent protein kinase II
reactive oxygen species
hypertrophy
apoptosis
spellingShingle Ciencias Médicas
angiotensin II
Ca2+-calmodulin-dependent protein kinase II
reactive oxygen species
hypertrophy
apoptosis
Vélez Rueda, Jorge Omar
Palomeque, Julieta
Mattiazzi, Alicia Ramona
Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
topic_facet Ciencias Médicas
angiotensin II
Ca2+-calmodulin-dependent protein kinase II
reactive oxygen species
hypertrophy
apoptosis
description The objective of this study was to establish whether 1) hyperactivity of renin-angiotensin-aldosterone system (RAAS) produces apoptosis in early stages of cardiac disease; and 2) Ca2+-calmodulin-dependent protein kinase II (CaMKII) is involved in these apoptotic events. Two models of hypertrophy were used at an early stage of cardiac disease: spontaneously hypertensive rats (SHR) and isoproterenol-treated rats (Iso-rats). At 4 mo, SHR showed blood pressure, aldosterone serum levels, used as RAAS activity index, and left ventricular mass index, used as hypertrophy index, above control values by 84.2 6 2.6 mmHg, 211.2 6 25.8%, and 8.6 6 1.1 mg/mm, respectively. There was also an increase in apoptotis (Bax-to-Bcl-2 ratio and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells) associated with an enhancement of CaMKII activity with respect to age-matched controls (phosphorylated-CaMKII, 98.7 6 14.1 above control). Similar results were observed in 4-mo-old Isorats. Cardiac function studied by echocardiography remained unaltered in all groups. Enalapril treatment significantly prevented hypertrophy, apoptosis, and CaMKII activity. Moreover, intracellular Ca2+ handling in isolated myocytes was similar between SHR, Iso-rats, and their aged-matched controls. However, SHR and Iso-rats showed a significant increase in superoxide anion generation (lucigenin) and lipid peroxidation (thiobarbituric acid reactive substance). In transgenic mice with targeted cardiomyocyte expression of a CaMKII inhibitory peptide (AC3-I) or a scrambled control peptide (AC3-C), Iso treatment increased thiobarbituric acid reactive substance in both strains, whereas it increased CaMKII activity and apoptosis only in AC3-C mice. Endogenous increases in RAAS activity induce ROS and CaMKII-dependent apoptosis in vivo. CaMKII activation could not be associated with intracellular Ca2+ increments and was directly related to the increase in oxidative stress.
format Articulo
Articulo
author Vélez Rueda, Jorge Omar
Palomeque, Julieta
Mattiazzi, Alicia Ramona
author_facet Vélez Rueda, Jorge Omar
Palomeque, Julieta
Mattiazzi, Alicia Ramona
author_sort Vélez Rueda, Jorge Omar
title Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
title_short Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
title_full Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
title_fullStr Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
title_full_unstemmed Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
title_sort early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves camkii
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/106764
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3774203&blobtype=pdf
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