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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2014
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oai:doaj.org-article:5cbb8f8fa17e45778c6cdaa14b0362ef2021-11-18T08:21:24ZIncreased Na⁺/Ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats.1932-620310.1371/journal.pone.0096400https://doaj.org/article/5cbb8f8fa17e45778c6cdaa14b0362ef2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24781001/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Jesica S RodriguezJ Omar Velez RuedaMargarita SalasRomina BecerraMariano N Di CarloMatilde SaidLeticia VittoneGustavo RinaldiEnrique L PortianskyCecilia Mundiña-WeilenmannJulieta PalomequeAlicia MattiazziPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e96400 (2014) |
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Medicine R Science Q 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. |
| 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 |
| 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 |
| title |
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_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_sort |
increased na⁺/ca²⁺ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/5cbb8f8fa17e45778c6cdaa14b0362ef |
| work_keys_str_mv |
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