Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats.
<h4>Unlabelled</h4>Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca²⁺-handling alterations are known to occur in SHR. However, the putative modifications of Ca²⁺-handling proteins during the prog...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096400&type=printable |
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| author | Jesica S Rodriguez J Omar Velez Rueda Margarita Salas Romina Becerra Mariano N Di Carlo Matilde Said Leticia Vittone Gustavo Rinaldi Enrique L Portiansky Cecilia Mundiña-Weilenmann Julieta Palomeque Alicia Mattiazzi |
| author_facet | Jesica S Rodriguez J Omar Velez Rueda Margarita Salas Romina Becerra Mariano N Di Carlo Matilde Said Leticia Vittone Gustavo Rinaldi Enrique L Portiansky Cecilia Mundiña-Weilenmann Julieta Palomeque Alicia Mattiazzi |
| author_sort | Jesica S Rodriguez |
| collection | DOAJ |
| description | <h4>Unlabelled</h4>Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca²⁺-handling alterations are known to occur in SHR. However, the putative modifications of Ca²⁺-handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca²⁺, Ca²⁺-handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca²⁺ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca²⁺ transient decay and an increase in Na⁺/Ca²⁺ exchanger (NCX) abundance (p<0.05) with no changes in SERCA2a expression/activity. An increased Ca²⁺-calmodulin-kinase II activity, associated with an enhancement of apoptosis (TUNEL and Bax/Bcl2) was observed in SHR relative to W from 3 to 15 mo.<h4>Conclusions</h4>1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca²⁺ efflux from the cell, constitutes a primary alteration of Ca²⁺-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident. |
| format | Article |
| id | doaj-art-5cbb8f8fa17e45778c6cdaa14b0362ef |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-5cbb8f8fa17e45778c6cdaa14b0362ef2025-08-20T02:14:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9640010.1371/journal.pone.0096400Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats.Jesica S RodriguezJ Omar Velez RuedaMargarita SalasRomina BecerraMariano N Di CarloMatilde SaidLeticia VittoneGustavo RinaldiEnrique L PortianskyCecilia Mundiña-WeilenmannJulieta PalomequeAlicia Mattiazzi<h4>Unlabelled</h4>Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca²⁺-handling alterations are known to occur in SHR. However, the putative modifications of Ca²⁺-handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca²⁺, Ca²⁺-handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca²⁺ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca²⁺ transient decay and an increase in Na⁺/Ca²⁺ exchanger (NCX) abundance (p<0.05) with no changes in SERCA2a expression/activity. An increased Ca²⁺-calmodulin-kinase II activity, associated with an enhancement of apoptosis (TUNEL and Bax/Bcl2) was observed in SHR relative to W from 3 to 15 mo.<h4>Conclusions</h4>1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca²⁺ efflux from the cell, constitutes a primary alteration of Ca²⁺-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096400&type=printable |
| spellingShingle | Jesica S Rodriguez J Omar Velez Rueda Margarita Salas Romina Becerra Mariano N Di Carlo Matilde Said Leticia Vittone Gustavo Rinaldi Enrique L Portiansky Cecilia Mundiña-Weilenmann Julieta Palomeque Alicia Mattiazzi Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. PLoS ONE |
| title | Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| title_full | Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| title_fullStr | Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| title_full_unstemmed | Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| title_short | Increased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| title_sort | increased na⁺ ca²⁺ exchanger expression activity constitutes a point of inflection in the progression to heart failure of hypertensive rats |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096400&type=printable |
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