INVESTIGADORES
MATTIAZZI Ramona Alicia
artículos
Título:
Increased na+/ca2+ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats.
Autor/es:
RODRIGUEZ JS; VELEZ RUEDA JO; SALAS M; BECERRA R,; DI CARLO MN; SAID M; VITTONE L; RINALDI GJ; PORTIANSKY E; MUNDIÑA WEILENMANN C; PALOMEQUE J; MATTIAZZI A
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2014 p. 96400 - 96410
ISSN:
1932-6203
Resumen:
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. Conclusions: 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.