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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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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I19-R120-10915-106764 |
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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 |
work_keys_str_mv |
AT velezruedajorgeomar earlyapoptosisindifferentmodelsofcardiachypertrophyinducedbyhighreninangiotensinsystemactivityinvolvescamkii AT palomequejulieta earlyapoptosisindifferentmodelsofcardiachypertrophyinducedbyhighreninangiotensinsystemactivityinvolvescamkii AT mattiazzialiciaramona earlyapoptosisindifferentmodelsofcardiachypertrophyinducedbyhighreninangiotensinsystemactivityinvolvescamkii |
bdutipo_str |
Repositorios |
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1764820443182661634 |