Alterations in sarcoplasmic reticulum ca2+ storing proteins in
pressure overload cardiac hypertrophy.
Tsutsui, Hiroyuki, Yuji Ishibashi, Kyoko Imanaka-Yoshida, Shimako
Yamamoto, Toshimichi Yoshida, Masaru Sugimachi, Yoshitoshi Urabe, and
Akira Takeshita.
Research Institute of Angiocardiology and Cardiovascular Clinic,
Faculty of Medicine, Kyushu University, Fukuoka 812, Department of
Pathology, Mie University, Tsu, Mie 514, and Department of
Circulatory Dynamics, National Cardiovascular Center, Suita, Osaka
565, Japan
APStracts 3:0331H, 1996.
The alterations of intracellular calcium (Ca2+) homeostasis may be
responsible for the contractile defects in pressure overload cardiac
hypertrophy. Ca2+-ATPase protein level of sarcoplasmic reticulum (SR)
is reduced in hypertrophied or failing heart. However, it is not
known whether Ca2+ storing proteins, including calsequestrin and
calreticulin, are also altered during cardiac hypertrophy. We
quantified SR Ca2+ regulatory proteins using Western blot analysis in
left ventricular (LV) muscle isolated from sham-operated control rats
(n = 6) and rats with pressure overload at 4 weeks after abdominal
aortic constriction (n = 7). Contractile function of isolated LV
myocytes, assessed by the sarcomere motion measured using laser
diffraction, was depressed in aortic constricted rats. SR Ca2+-ATPase
protein level was decreased to 56 +/- 9 (mean +/- SE) % of control (p
< 0.01) in hypertrophied myocardium. Calsequestrin protein level
was not altered, whereas calreticulin was increased by 120 +/- 3 % of
control (p < 0.05) in aortic-constricted rats. The alterations
of SR Ca2+ regulatory proteins were equally observed in hypertrophied
hearts even when the results were normalized using the amounts of
myosin heavy chain proteins in each sample. Immunohistochemical
staining of calsequestrin in the control heart showed the cross
-striations at the Z-lines, whereas calreticulin was hardly observed
within myocytes but was intense within interstitial fibroblasts. In
the hypertrophied heart, calreticulin was observed at the perinuclear
region within the myocyte cytoplasm. These data indicate that
pressure overload cardiac hypertrophy causes the alterations in SR
Ca2+ storing proteins as well as Ca2+-ATPase, which may contribute to
the contractile dysfunction of the hypertrophied myocytes.
Received 22 January 1996; accepted in final form 15 July 1996.
APS Manuscript Number H55-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996