Biochemistry of Hypertrophy and Heart Failure

156 Pages·2003·9.89 MB·English

by  Danny P. Goel, David A. Ford (auth.), Lorrie A. Kirshenbaum, Ian M. C. Dixon, Pawan K. Singal (eds.)

BIOCHEMISTRY OF HYPERTROPHYANDHEART FAILURE
Biochemistry of Hypertrophy and
He art Failure
Edited by
LORRIEA. KIRSHENBAUM IAN M.C. DIXON
Institute of Cardiovascular Sciences Institute of Cardiovascular Sciences
St. Boniface General Hospital St. Boniface General Hospital
Research Center Research Center
351 Tache Avenue Room 3038 SBGH Research Center
Winnipeg, Manitoba R2H 2A6 351 Tache Avenue
Canada R2H 2A6, Winnipeg, Manitoba
Canada
PAWAN K. SINGAL
Institute of Cardiovascular Sciences
St. Boniface General Hospital
Research Center
Faculty ofMedicine
University of Manitoba
Winnipeg, Manitoba R2H 2A6
Canada
Reprinted from Molecular and Cellular Biochemistry, Volume 25 I (2003)
Springer Science+Business Media, LLC
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DOI 10.1007/978-1-4419-9238-3
Copyright © 2003 by Springer Science+Business Media New York
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Molecular and Cellular Biochemistry:
An International Journal for Chemical Biology inHealth and Disease
CONTENTS VOLUME 251, Nos. 1 & 2, September 2003
BIOCHEMISTRY OF HYPERTROPHY AND HEART FAILURE
Drs. Lorrie A. Kirshenbaum, Ian M.e. Dixon and Pawan K. Singal
Preface I
D.P. Goel, D.A. Ford and GN. Pierce : Lysoph osphol ipids do not directly modulate NA +-W exchange 3- 7
N. Khaper , K. Kaur, T. Li, F. Farahmand and P.K. Singal : Antioxidant enzyme gene expression in conge stive hear t failure following
myoc ardial infarction 9- 15
F. Villarreal, S. Zimmerma nn, L. Makhsudova, A.C. Montag, M.D. Erion, D.A. Bullough and B.R. Ito: Modulation of cardiac remodeling
by adenosine : In vitro and in vivo effects 17-26
T.H.F. Peters , P.L. de Jong , L. Klompe, R.M.F. Berger, P.R. Saxena, H.S. Sharma and AJJ.C. Bogers : Right ventricu lar collagen and
fibro nec tin leve ls in patients with pulmonary atres ia and vent ricular septal defec t 27-32
R. Prabhakar, N. Petrashev skaya, A. Schwartz, B. Aronow, GP. Boivin, J.D. Molkent in and D.F. Wieczorek : A mouse model of familial
hypertrophic cardiomyopathy caused by a a -tropomyosin mutation 33-42
K. Kato, M. Kodama, S. Hirono, Y. Okura, H. Hanawa , T. Shio no, M. Ito, K. Fuse , K. Tsuchida, S. Maruyama, T. Yoshida, S. Abe, M.
Hayashi , A. Nasuno , T. Saiga wa, T. Ozawa , Y. Aizawa: Analysis of postextrasystolic relaxation response in the human heart 43-46
J.R. Pollack , R.C. Witt and J.T. Sugimo to: Differentia l effect s of calpain inhibitors on hypert rophy of cardiomyoc ytes 47-50
A. Fenning , G Harrison, D. Dwyer, R. Rose 'Meyer and L. Brown: Cardiac adaptation to endurance exerc ise in rats 5 1-59
M.M. Lalu, C.Q. Gao and R. Schulz: Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: A potential
role for MMP-9 61-66
G Wallukat, S. Podlowski, E. Nissen , R. Morwinski, C. Csonka, A. Tosaki and I.E. Blasig : Functional and structural charac terization
of anti-B I -adrenoceptor autoantibodies of spontaneo usly hypertensive rats 67-75
W. Juan, M. Nakazawa, K. Watanabe, M. Ma, M.I.I. Wahed, G Hasegawa , M. Naito, T. Yamamoto, K. Fuse, K. Kato, M. Kodama and
Y. Aizawa : Quinapril inhibit s progression of heart failure and fibrosi s in rats with dilated cardiomyopathy after myocardities 77-82
J. Barta , A. Toth, K. Jaquet, A. Redlich, I. Edes and Z. Papp: Calpain-l -depende nt degradation of troponin I mutants found in familial
hypertrophic cardiomyopathy 83-88
G L. Brower, J.D. Gardn er and J.S. Janicki: Gender media ted cardiac protection from adverse ventricular remodeling is abol ished by
ovariec tomy 89-95
A. Sabri and S.F. Steinberg: Prot ein kinase C isoform-selective signals that lead to cardiac hypertrophy and the progression of heart
failure 97- 10 1
B. Chaudhri , F. del Monte, RJ . Hajjar and S.E. Harding: Contract ile effects of adenovirally-mediated increases in SERCA2a activity:
A comparison betwee n adult rat and rabb it ventricu lar myocytes 103- 109
M.L. Zhang , S. Elkas sem, A.W. Davidoff, K. Saito and H.E.DJ . ter Keurs: Losartan inhibits myosin isoform shift after myocardial
infarction in rats 1 11-11 7
M. Leic ht, G Marx , D. Karbach, M. Gekle , T. Kohler and H.-G. Zimmer: Mechanism of cell death of rat cardiac fibrob lasts induced
by serum depletion 119 -126
A. Deten, H.C. Volz, A. Holzl, W. Briest and H.-G Zimmer: Effec t of propranolol on cardiac cytoki ne exp ression after myocardia l
infarct ion in rats 127-1 37
C. Ocampo , P. Ingram, M. Ilbawi, R. Arcilla and M. Gupta : Revisiting the surgical creation of volume load by aorta-caval shunt in rats 139- 143
N. Buscemi, A. Doherty-Kirby, M.A. Sussman, G Lajo ie and J.E. Van Eyk : Proteomic analy sis of Racl tran sgenic mice displaying
dilated car diomyo pathy reveals an increase in creatine kinase M-chain protein abund ance 145- 151
M. Donato and R.J. Gelpi: Adenosi ne and card ioprotect ion during repe rfusion - an overv iew 153- 159
Ind ex to Volume 251 161 -1 63
ii;wed/tJl1tJ&
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Molecular and Cellular Biochemistry 251: J. 2003 .
© 2003 Kluwer Academic Publishers. Printed in the Netherlands .
Preface
Heart failure representsa major financialand socio-economic suit in ventricularremodeling anddiminishedcardiacperform-
burden worldwide as patients diagnosed with this form of ance. Thus chronic cardiac hypertrophy ultimately is closely
heart disease require costly medical treatments and chronic associated with end-stage heart failure and death.
long-term care. Despite the substantial progress made dur- The manuscripts included in this volume present basic re-
ing the past two decades of heart research, cardiac disease search that address the fundamental basis of heart hypertro-
remains a prominent cause of death along with cancer and phy and heart failure.This work wascontributed by scientists
infectious diseases. In North America heart disease accounts who had attended the XVII World Congress of the Interna-
for about 45% of all deaths. A chronic increase in cardiac tional Society for Heart Research held in Winnipeg, Canada
workload imposed by valvular defects, uncontrolled hyper- July,200I. The focusof this issue is on the underlyingmecha-
tension, and coronary artery disease is accompanied by car- nismsthatregulatecardiacgrowth. Thisnewinformation could
diac and neurohumoral adjustments. One of the prominent ultiinately be used for the design of new treatment modalities
features ofchronicheartdiseaseis growthof cardiacmyocytes to reduce the incidence of cardiac failure, thereby improving
(both adaptive and aberrant) itself contributing directly to quality of life in patients with heart chronic heart disease.
heart hypertrophy. Biochemical reprogramming of the myo-
cardium occurs from altered gene expressionat the level of LorrieA. Kirshenbaum, IanM.e. DixonandPawanK.Singal
thecardiacmyocyteandfibroblast/myofibroblast populations; Institute of Cardiovascular Sciences
the latterdirectlyinfluencesthe natureof cardiacextracellular St. Boniface General Hospital Research Centre
matrix. These molecular, cellular and subcellularchanges re- Winnipeg, Manitoba
Canada
Molecular and Cellular Biochemistry 241: 3-7,2003 .
© 2003 Kluwer Academic Publishers. Printed in the Netherlands.
Lysophospholipids do not directly modulate Na+-H+
exchange
l 1
Danny P. Goel, DavidA. Ford? and Grant N. Pierce
'Cell Biology Laborato ry, Division ofStroke and Vascular Disease; The National Centre for Agri-fo od Research in
Medicine, St. Boniface General Hospital Research Centre; Department ofPhysiology, Faculty ofMedicine,
University ofManitoba, Winnipeg, Man itoba, Canada ; "Schaol ofMedical Biochemi stry, St. Louis Universi ty, St. Lou is,
MO, USA
Abstract
Lysophosphatidylcholine (LPC) has been reported to stimu late Na+-H+ exchange in rat cardiomyocytes. This action may be
important in pathological conditions like ischemic injury where LPC is generated and Na+-H+exchange activation is an impor-
tant determinant of cardiac damage and dysfunction. It is unclear, however, if this stimulation of Na+-W exchange by LPC
occurs throu gh a direc t action on the exchanger or through stimulation of a second messenger pathway. The purpose of the
present investigation was to determine iflysolipids could directly affect Na+-W exchange. Purified cardiac sarcolemmal mem-
branes were isolated and Na+-H+exchange was measured by radioisotopic methods following addit ion of LPC. There were no
effect s of LPC on Na+-H+ exchange at LPC concentrations of s 100 flM at all reaction time s examined. Lysophosphatidyl-
ethanolamine (LPE) , Iysopho sphatidylserine (LPS), Iysophosphatidylinositol (LPI) and Iysoplasmenylcholine (LPEC) also did
not alter Na+-H+ exchange at all conc entrations and reaction time s exam ined . We conclude that any stim ulatory effects of
lysolipids on Na+-H+exchange do not occu r through a direct action on the exchanger or its membrane lipid envi ronment and
must occur through a second messenger pathway. (Mol Cell Biochem 241 : 3-7, 2003)
Key words: lysophosphatidylcholine, sarcolemma, ischemia, heart, sodium-proton exchange
Introduction it is uncle ar if LPC does alter Na+-H+exchange and if so,
through what mechani sm. It is possible that lysolip ids may
Lysopho sphatidylcholine (LPC) levels are elevated follow- directly alter Na+-H+ exchange activity. Many of the ion trans-
ing cardiac ischemia [1-6] . This is important because LPC port proteins identified abo ve are altered via a direct action
is thought to be a mediator of ischemia-induced arrhythmias of LPC on the protein or the phospholipid environment sur-
[7-10]. LPC is known to affect the activity of a number of rounding the transporter. Howe ver, Hoque et al. [19] hypoth-
ion transporters. LPC affects cardiac Na' channels [11-13], esized that LPC stimulation of Na+-H+exchange occurred via
K+channels [14, IS], and inhibits the Na+-K+ ATPase [16, 17] a protein kinase pathway. This is a plausible proposal because
and the Na+-HC03- transporter [18] . The Na+-H+ exchanger lysolipids are known to stimulate myocardial protein kinases
is another ion transporter in the heart that is a key modulator [25].
of ischemic dam age and dysfunction [19-2 1]. Hoque et al. The rationale for this study was, therefore , to determine if
reported a stimulation of Na+-H+ exchange in rat cardio- the addition of exogenous LPC would have a direct effect on
myocyte s following LPC addition [19]. However, Yamaguch i Na+-H+ exch ange. We used purifi ed sarcolemmal vesicles to
et al. reported no effect of LPC on the Nat-H rexchanger in eliminate the possibility that a second messenger system (like
cardiomyocytes [18]. Na+-W exch ange has been reported to a kina se) would have any effect on exchange. We also ex-
be unaffecte d by its pho spholipid environment [18, 22] al- amined the po tential for other lysol ipids like lysophos-
though this has been contested by others [23, 24]. Therefore , phatidylethan olamine (LPE) , lysophosphatidylserine (LPS) ,
Address for offp rints: G N. Pierce, Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, 35\ Tache Avenue , Winnipeg,
Manitoba, Canada, R2H 2A6 (E-mail:
4
lysophosphatidylinositol (LPI) and lysoplasmenylcholine vortexing the mixture. Final assay concentrations were 180 mM
(LPEC) to alter Na+-H+exchange. This is presently unknown. sucrose, 10mM Mes, 17.5 mM Ches, 17 mM KOH, 0.05 mM
EGTA and 0.05 mM Na+at a final extravesicular pH of9.33.
Calibration of all assa y media was done carefully using an
Orion 82-10 pH electrode to ensure accuracy. Following a
Materials and methods
preset time (2-5 sec), 3 mL of stop solution (100 mM KCI,
20 mM Hepes, pH 7.5) was added to the polystyrene tube to
Materials
arrest the reaction. The reaction mixture was filtered rapidly
through 0.45 11m Millipore filters, followed by an additional
The Millipore filters , thin layer chromatography plates and
2 x 3 mL wash with the same stop solution. Filters were re-
organic solvents were supplied by Fisher Scientific. The 22Na
moved, placed in scintillation vial s, dried and radioactivity
was purchased from NEN Life Sciences. Lysophosphatidyl-
quantitated using scintillation spectroscopy. Blanks were
choline, lysophosphatidylethanolamine, lysophosphatidyl-
treated in a similar manner except 3 mL ice-cold stop solu-
serine and lysophosphatidylinositol were supplied by Doosan
tion was added immediately prior to the inclu sion of 20 ul,
Serdary, Toronto, Ontario. Lysoplasmenylcholine was syn-
sarcolemmal protein.
thesized as described previously (reference).
Treatment with lysophospholipids
Sarcolemmal membrane preparations
Severallysophospholipids were incubated with sarcolemmal
Pigs (65-85 kg) were anae sthetized with Telazol (20 mg/mL)
vesicle s between I and 11 min . Lysophospholipids were sus-
using a dose of I mL/23 kg animal body weight. Hearts were
pended in 200 mM sucrose, 25 mM Mes and 8 mM KOH (pH
removed and cardi ac sarcolemmal vesicles were harvested
5.5) to yield a final concentration of 10 mM Iysophospholipid.
from the left ventri cle as described previously [26] . Purity of
This was diluted 100-1000 fold to yield final concentrations
these sarcolemmal vesicles was determined using specific
of 10, 25, 50 and 100 11M Iysophospholipid. Pre-incubation
marker assays. The Kt-p-nitrophenyl phosphatase assay and
of lysopho spholipids was carried out over 3 min with a subse-
the Na+-K+ ATPase assay are described elsewhere in detail
quent Na' uptake time of 2, 5 and 30 sec .
[26]. Kt-stimulated p-nitrophenyl phosphatase activity was
12 ± 21lmol phenol/mg per h in the sarcolemmal fraction (n
= 7). Similarly, Na+-K+ATPase activity in this sarcolemmal
fraction was II ± 3 and 35 ± 10 umol Pi/mg per h in the ab- Statistics
sence and presence of 12.5Ilg/mL alamethicin, respectively.
These activities were enriched in the sarcolemmal vesicles Data are expressed as mean ± S.E. Statistical dete rmination
- 100 fold when compared to homogenate. The sarcolemmal was done using a Students t- test and was considered signifi-
membrane-enriched final fraction was diluted into a suspen- cant at p < 0.05.
sion medium containing 200 mM sucrose , 25 mM Mes , 8 mM
KOH , pH 5.5 and centrifuged for 2 h at 175,000 x g. The
pelleted membranes were resu spended in the same suspen-
Results
sion medium at a protein concentration of 1-3 mg/mL.
Protein concentrations were determined using the method
The effect of LPC on the activity of the Na+-H+ exchanger
described previously [26, 27]. These samples were frozen in
was examined. Different concentrations of LPC (10 , 25 50
liquid N , and stored at -80°C for subsequent analysis.
2
and 100 11M LPC) were incubated with sarcolemmal vesicles .
Figure I shows no statistically significant difference in W-
Measurement of Na: -H+ exchange dependent Na' uptake at any concentration of LPC examined.
When Na+-H+ exchange was examined over various reac-
Ht-dependent Na" uptake was examined in control vesicles tion times (2-30 sec), no concentration ofLPC produced a
and those treated with Iysophospholipids, as described else- statistically significant change in Na+-H+ exchange activ-
where in detail [23,24,27,28]. Briefly, 5 ul, of 22Na (O.IIlCi) ity (Fig . 2) .
was added to the bottom of a polystyrene tube containing 25 The effects of plasmalogen LPC, LPEC, on Na+-H+ ex-
ul, uptake medium, 200 mM sucrose, 30 mM Ches, 40 mM change activity were also examined. At concentrations of 10,
KOH , 0.1 mM EGTA and 0.1 mM Na+ (pH 10.61) . A 20 ilL 25,50 and 100 11M LPEC, there was no change in Na+-H+ex-
aliquot of sarcolemmal membrane protein (II ug) was placed change activity (Fig. 3). This finding was con sistent acro ss
on the side of the tube and Nat-Ht exchange was initiated by variable reaction times (Fig. 4) .
5
120 120
100 100
" SO " so
!
Z± ~ 60 %;.~-: ~- 60
~::": ~ =" -10
-]:9. ;- -10 .:~;.~- 20
:.. 20 .±
0
0 control to 25 50 100
control 10 25 50 100 Lysophosph utidylcholine (11 ;\1)
Lysoph osphat idylcholi ne (11;\I )
Fig. 1. Hr-dependenr Na" uptake in LPC treated sarcolemmal vesicles . Fig. 3. Ht-dependeru Na' uptake in LpeC treated sarco lemmal vesicles.
Sarco lemmal vesicles were pre-incub ated with 10, 25, 50 and 100 11M LPC Sarcolemmal vesicles were pre-incubated with 10, 25, 50 and 100 11M of
for 3 min. Ht-dependent Na" uptake was exami ned for 5 sec in pH 10.61 at LPeC for 3 min in pH 5.5 , T =25°C. Hr-dependent Na' uptake was exam -
25°C. ined for 5 sec in pH 10.6 1, [Na'] 0.05 mM.
Tofurtheranalyzethe dependence of the Na+-H+ exchanger min. Incubation with LPS, LPI and LPE produced no statis-
on membrane phospholipids, a number of Iysophospholipids tically significant changes in Na+-W exchange activity (Fig.
wereincubated with sarcolemmal vesicles. LPS, LPI andLPE 5).When examined at variable reaction times, the results were
were pre-incubated with cardiac sarcolemmal vesicles for 2 similar (Fig. 6).
-It- control -It- control
2
2.42 -.ItTt.--IO5250II1Il1MM 1.4 -I4t- 2150 11M
2.0 -+-IOOIlM 1.2 -T- 50 11M I
.:.: 1.8 .<:.:II -+- 100 11M
Q'".. 1.6 SCl. 1.0
:"'z+.<9<='e=<=.0".I,I:o:Se=:I:n. ~ 0
01.486024 :".+=e='<i.0z".I,Ii:~:a=C<~:>J.l 0.4268 f!1'
0.2 "
0.0 0.0
a 5 10 15 20 25 30 0 5 10 15 20 25 30
Reaction Ti me (seconds)
Reaction Time (seconds)
Fig. 2. Hr-dependent Na" uptake in LPC treated vesicles as a funct ion of Fig. 4. W dependent Na" uptake in LpeC treated sarcolemmal vesicles as a
reaction time . Sarco lemmal vesicles were pre-incubated with 50 11M LPC function of reaction time and [LpeC]. Sarcolemmal vesicles were pre-incubated
for 3 min at pH 5.5, T =25°C. Reaction was carried out in pH 10.6 1 media with 10,25 ,50 and 100 11M LpeC for 3 min in pH 5.5, T =25°C. W-dependent
for 2, 5 and 30 sec, [Na"], = 0.05 mM. Na' uptake was examined at 2, 5 and 30 sec in pH 10.61, [Na"] 0.05 mM.
6
at. [19] have shown that LPC stimulated NHE-1 in cardio-
100 myocytes. However, Yamaguchi et at. reported no effec t of
LPC on the cardiac Na'-Htexchanger [18]. Therefore, it is
so unclear if LPC does alter Na"-W exchange. If it does stimu-
:..
late Na'- H+exchange, three potential mechanisms may ac-
1 60 count for this action . LPC may alter Na+-H+ exchange via :
..
Z (i) a direct effect on the exchanger or, (ii) through an indi-
~= <:-:; -\0 rect signa ling mechanism, or (iii) via some comb ination of
~ t;": both of these effects. Hoque et at. [19] hypothesized that LPC
f ~() stimulation of Na+-H+exchange occurred via a protein kinase
- pathway. To address the direct effect oflysolipids on the Nat-
() H+ exchange r, we have examined the effects of LPC in iso-
control LPS LI'J lY E lated sarcolemmal membranes instead of cardiomyocytes.
Using a sarco lemmal membrane preparation removes the in-
Lysophuspholipid s
fluence of kinases or other secon d messengers. In our study,
Fig. 5 . Hr-dependent Na" uptake as a funct ion of variable lysophospho- there was no effect of LPC on the cardiac sarcolemmal Na"-
lipids. Sarcolemmal vesicles were pre-incubated with 50 f.lM LPS, LPI and H+exchanger. This finding was not restricted to only one
LPE for 2 min. Na" uptake was examined in a final solution consisting of species of Iyso lipid . Lyso phosphatidylcholine, Iysopl as-
0.05 mM Na", pH 9.33 for 5 sec. Data are represented as mean ± S.E. of 3 menylcholine, Iysophosphatidylserine, lyso phosphatidy l-
separate experiments.
inosi tol and lysophosphat idylethanolamine all had no effect.
Furthermore, phospholipase A2, which generates LPC, had
no effect on sarcolemmal Na+-H+exchange (data not shown).
Discussion The concentrations of lyso lipids that were employed in this
study (up to 100 11M) are thought to be relevant to the patho-
Inhibitory effects of LPC have been reported on several ion logical state [32, 33]. We can conclude, therefore, that our
transport pathways including Na+-Ca2+exchange [29], the data strongly rule out Iysolipids as direct modul ators of car-
Na+-K+ATPase [16, 17, 30], Na' channels [12, 13], K+chan- diac sarcolemmal Na+-H+ exchange in both in vitroand in vivo
nels [14, 15,31 ] and the Na+-HC03- transporter [18]. The ef- settings.
fect oflysolipids on Na+-H+exchange is less clear. Hoque et The length of the fatty acid carbo n chain could contribute
to the inabili ty of these Iysolipids to alter Na+-W exchange
function. Long chain fatty acids (like eicosapentanoic acid,
- - cont rol docosahexa noic acid and arachidonic acid) significa ntly al-
2.0 -.- LPS ter NHE activity whereas shorter chain fatty acids (linolenic
-~ LPI and linoleic acid) are ineffective [24]. LPC, LPE, LPEC, LPS
1.8
-...- LPE and LPI all contain very short carbon chains. Thus, the re-
~
..es., 1.46 sutrlutsc tsuhroew/funnhcetiroenwrietlhatihoenIsyhsiopl.ipids are consistent with this
+.=.;:.0;.- 1.2
theOduiresctuedfyfe,cthtseroeffionrdei,vids uthalepfuirrset IiynsvoelsiptigdastoionncatordeivacalNuat"e-
"z-.
50=..~.-"0=. 01.80 tHh+eseexclihpaindgse.onONura+re-Hsu+ltesxchleaanrlgye.ruAlenyoustima udilraetcotryefefefcfetcotsf
:'+9~: ~ 0.46 Imt uwsitllocbceuorfthinroteurgehstainsethceonfdutmurestsoenidgenr-tmifyediifaittedispiantdhewedaya.
kinase and if this stim ulation is specific for one part icular
0.2 kinase.
0.0
0 5 10 15 20 25 30
Reaction Time (seconds)
Acknowledgements
Fig. 6. Time course in Ht-dcpendent Na" uptake in LPS, LP I and LPE
treated sarcolemmal vesicles. Sarcolemmal vesicles were pre-incubated with
50 f.lM LPS, LPI and LPE for 2 min at 25°C (pH 5.5). Na+uptake was ex- This study was supported by a grant from the Heart and Stroke
amined in a final solution consisting of 0.05 mM Na', pH 9.33. Data are Foundation of Manitoba. GN Pierce is a Senior Scien tist of
represented a mean + S.E. of separate experimen ts. the Canadian Institutes for Health Research.
7
dog heart sarcolemma by Iysophosphatidyl choline. Life Sci 24: 1869-
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