Regression of isoproterenol-induced cardiac hypertrophy

1984 ◽  
Vol 62 (9) ◽  
pp. 1141-1146 ◽  
Author(s):  
Qian Tang ◽  
Paul B. Taylor
Keyword(s):  
Cardiac Hypertrophy ◽  
Recovery Period ◽  
Control Level ◽  
Weight Ratio ◽  
Heart Weight ◽  
Half Time ◽  
Body Weight Ratio ◽  
Subcutaneous Injections ◽  
Rna Content ◽  
Female Wistar Rats

Cardiac hypertrophy was induced in adult female Wistar rats after 8 days of daily subcutaneous injections of isoproterenol (ISO). Regression from hypertrophy was studied following 1, 2, 4, 8, 12, and 20 days of ISO withdrawal. After 8 days of treatment cardiac mass increased 40%. Following ISO withdrawal, ventricular regression occurred during the first 8 days. After 12–20 days of recovery, a new steady-state heart weight to body weight ratio was established that was 12–13% above the controls. The half-time recovery for heart weight was 3.8 days. Ventricular RNA content was stimulated 76% after 8 days of ISO-induced hypertrophy. During regression RNA content decreased rapidly during the first 8 days with a half-time of 3.4 days. Following 20 days of recovery ventricular RNA was still 31% above the controls. However, myocyte RNA was stimulated 86% following 8 days of ISO treatment and returned to control level after 12 days of regression. Myocardial DNA was increased 23% in the hypertrophied hearts and did not change during the recovery period. Hydroxyproline was increased in the ISO-treated hearts and decreased only slightly during the recovery interval. These data indicate that ISO-induced hypertrophy was reversible while ventricular RNA content only partially recovered. Nevertheless, myocyte RNA showed a large stimulation that was completely reversible at least after 12 days of recovery.

Exercise conditioning increases rat myocardial calcium uptake

1986 ◽  
Vol 60 (5) ◽  
pp. 1673-1679 ◽  
Author(s):  
S. N. Levine ◽  
G. T. Kinasewitz
Keyword(s):  
Body Weight ◽  
Sarcoplasmic Reticulum ◽  
Adrenergic Receptors ◽  
Calcium Uptake ◽  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Heart Weight ◽  
Scatchard Analysis ◽  
Body Weight Ratio ◽  
Female Wistar Rats

To investigate potential mechanisms underlying the enhanced myocardial performance consequent to exercise training, the adrenergic receptors of myocardial tissue and Ca2+ uptake into sarcoplasmic reticulum-enriched fractions from exercise conditioned animals were compared with that of sedentary controls. Female Wistar rats were exercised by swimming 30 min (5 days/wk) for 12 wk. Exercise conditioning was effective in producing myocardial hypertrophy, as reflected by an increase in heart weight (1.179 +/- 0.022 vs. 1.031 +/- 0.020 g, P less than 0.001) and heart weight-to-body weight ratio (3.29 +/- 0.06 vs. 2.77 +/- 0.05 X 10(-3), P less than 0.001) but no difference in body weight. Despite the myocardial hypertrophy, neither the affinity nor the density of the alpha 1-adrenergic receptors or the beta-adrenergic receptors determined by Scatchard analysis of the ligands [3H]prazosin and [3H]dihydroalprenolol were significantly different between the two groups. The basal Ca2+ uptake into the sarcoplasmic reticulum was also similar (9.90 +/- 0.97 vs. 9.04 +/- 0.75 nmol/mg protein/min), but the addition of calmodulin produced a significantly greater increment in Ca2+ uptake into sarcoplasmic reticulum from the exercised-conditioned animals (1.90 +/- 0.23 vs. 1.21 +/- 0.19 nmol/mg protein/min, P less than 0.03). The adenosine triphosphatase (ATPase) activities of the sarcoplasmic reticulum-enriched fractions of the two groups were similar. We conclude that exercise conditioning produces an enhancement of calmodulin-mediated calcium uptake that is independent of any effect on Ca2+-ATPase.

NF-κB activation is required for the development of cardiac hypertrophy in vivo

2004 ◽  
Vol 287 (4) ◽  
pp. H1712-H1720 ◽  
Author(s):  
Yuehua Li ◽  
Tuanzhu Ha ◽  
Xiang Gao ◽  
Jim Kelley ◽  
David L. Williams ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Weight Ratio ◽  
Dominant Negative ◽  
Heart Weight ◽  
Dominant Negative Mutant ◽  
Body Weight Ratio ◽  
Aortic Banding ◽  
Important Target

In the present study, we examined whether NF-κB activation is required for cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic banding for 1, 3, and 5 days and 1–6 wk, and age-matched sham-operated rats served as controls. In a separate group of rats, an IκB-α dominant negative mutant (IκB-αM), a superrepressor of NF-κB activation, or pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-κB activation, was administered to aortic-banded rats for 3 wk. The heart weight-to-body weight ratio was significantly increased at 5 days after aortic banding, peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA expressions were significantly increased after 1 wk of aortic banding, reached a maximum between 2 and 3 wk, and remained increased at 6 wk compared with age-matched sham controls. NF-κB activity was significantly increased at 1 day, reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-β activity was significantly increased at 1 day, peaked at 5 days, and then decreased but remained elevated at 6 wk after aortic banding compared with age-matched sham controls. Inhibiting NF-κB activation in vivo by cardiac transfection of IκB-αM or by PDTC treatment significantly attenuated the development of cardiac hypertrophy in vivo with a concomitant decrease in NF-κB activity. Our results suggest that NF-κB activation is required for the development of cardiac hypertrophy in vivo and that NF-κB could be an important target for inhibiting the development of cardiac hypertrophy in vivo.

Development of isoproterenol-indueed cardiac hypertrophy

1984 ◽  
Vol 62 (4) ◽  
pp. 384-389 ◽  
Author(s):  
Paul B. Taylor ◽  
Qian Tang
Keyword(s):  
Cardiac Hypertrophy ◽  
Dna Content ◽  
Time Course ◽  
Early Stage ◽  
Phase 1 ◽  
Heart Weight ◽  
Half Time ◽  
Hypertrophic Growth ◽  
Rna Content ◽  
Days Of Therapy

The development of cardiac hypertrophy was studied in adult female Wistar rats following daily subcutaneous injections of isoproterenol (ISO) (0.3 mg/kg body weight). A time course was established for the change in tissue mass, RNA and DNA content, as well as hydroxyproline content. Heart weight increased 44% after 8 days of treatment with a half time of 3.4 days. Ventricular RNA content was elevated 26% after 24 h of a single injection and reached a maximal level following 8 days of therapy. The half time for RNA accumulation was 2.0 days. The total content of hydroxyproline remained stable during the first 2 days of treatment but increased 46% after 4 days of therapy. Ventricular DNA content was unchanged during the early stage (1–4 days) of hypertrophic growth but increased to a new steady-state level 19% above the controls after 8 days of treatment. Intraventricular pressures and coronary flow measures were similar for control and experimental animals following 4 days of developed hypertrophy. However, dP/dt in the ISO-treated hearts was slightly but significantly (P < 0.05) elevated. These data indicate that the adaptive response to ISO shows an early hypertrophic phase (1–4 days) characterized by a substantial increase in RNA content and cardiac mass in the absence of changes in DNA. However, prolonged stimulation (8–12 days) appears to represent a complex integration of both cellular hypertrophy and hyperplasia within the heart.

scholarly journals Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoying Zhang ◽  
Zhiying Zhang ◽  
Pengxiang Wang ◽  
Yiwei Han ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Cardiac Hypertrophy ◽  
Heart Function ◽  
Weight Ratio ◽  
Tibetan Medicine ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Body Weight Ratio ◽  
Cross Sectional

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.

Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

2019 ◽  
Vol 116 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Hairuo Lin ◽  
Yang Li ◽  
Hailin Zhu ◽  
Qiancheng Wang ◽  
Zhenhuan Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cardiac Remodelling ◽  
Heart Weight ◽  
Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

scholarly journals PO-148 Effect of Aerobic Exercise on the Expression of CaMKIIδ/MEF2 in Hypertensive and Physiological Cardiac Hypertrophy

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Man Zhu ◽  
Lijun Shi
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Aerobic Exercise ◽  
Weight Ratio ◽  
Exercise Group ◽  
The Body ◽  
Expression Level ◽  
Heart Weight ◽  
Control Group ◽  
Body Weight Ratio

Objective The type II calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) signal plays a key role in the development of cardiac hypertrophy. This study used CaMKIIδ as an entry point to investigate the mechanism of moderate-intensity aerobic exercise affecting myocardial function. Methods Male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs), 12 weeks age, were randomly divided into aerobic exercise group (SHR-EX/WKY-EX) and sedentary control group (SHR-SED/WKY-SED), with 12 rats in each group. The aerobic exercise group conducted an 8-week treadmill exercise training with a slope of 0°, 20m/min (about 55-65% of maximal aerobic velocity), 60min/day, and 5d/wk. The control group did not exercise. The body weight of each group of rats was measured weekly and the blood pressure of the rats was measured non-invasively. After 8 weeks, the hearts of SHR-EX group, WKY-EX group, SHR-SED group and WKY-SED group were weighed, and then myocardial tissue sections were taken for HE staining to observe the thickness of the ventricular wall and the morphology of myocardial cells. The expression of CaMKIIδ and MEF2 in each group was determined by Western blotting. Results (1) The body weight of SHR-SED group was significantly higher than that of SHR-EX group (p<0.01), and the heart weight of rats in exercise group changed significantly. The WKY-EX group had greater heart weight than the WKY-SED group, and the SHR-SED group was heavier than the SHR-EX group (p<0.05). The heart weight/body weight ratio of the WKY-EX group was significantly higher than that of the WKY-SED group (p<0.01). The heart weight/body weight ratio of SHR-EX group and SHR-SED group was higher than that of WKY-EX group and WKY-SED group (p<0.01). (2) Compared with the WKY-SED group, the SHR-SED group had loose interstitial cells and increased single cell area. The SHR-EX group is more compact than the SHR-SED group, and the cell cross-sectional area is reduced. (3) The expression of CaMKIIδ protein in SHR-EX group was significantly lower than that in SHR-SED group (p<0.01), but the expression level of CaMKIIδ in WKY-EX group was significantly higher than that in WKY-SED group (p<0.01). The expression level of CaMKIIδ was significantly higher in the SHR-SED group than in the WKY-SED group. In addition, the expression of MEF2 protein in SHR-EX group and WKY-SED group was significantly lower than that in SHR-SED group (p<0.01), while the MEF2 expression level in WKY-EX group was higher than WKY-SED group and SHR-EX group (p<0.05). Conclusions There is an interaction between aerobic exercise and hypertension. Aerobic exercise can effectively delay the development of hypertensive cardiac hypertrophy by regulating the expression of CaMKIIδ and MEF2 protein in the myocardium, but it can also cause cardiac hypertrophy in normal heart. It is one of the important mechanisms affecting the myocardial morphology and function.    

ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice

1994 ◽  
Vol 266 (6) ◽  
pp. H2468-H2475 ◽  
Author(s):  
H. A. Rockman ◽  
S. P. Wachhorst ◽  
L. Mao ◽  
J. Ross
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Heart Weight ◽  
Receptor Blockade ◽  
Body Weight Ratio

There is increasing evidence that the renin-angiotensin system may play a important role in cardiac hypertrophy. To assess the role of angiotensin II in the induction of cardiac hypertrophy, three groups of adult mice were subjected to left ventricular pressure overload by transverse aortic constriction (TAC). For the next 7 days the groups received either the specific angiotensin II subtype 1 receptor (AT1) antagonist (losartan, 1.05 g/l; n = 17), an angiotensin enzyme inhibitor (captopril, 2 g/l; n = 17), or no treatment (n = 22) administered in the drinking water and compared with three similarly treated sham-operated groups (n = 7 each). TAC resulted in a significant increase in heart weight-to-body weight ratio (0.634 +/- 0.087 vs. 0.525 +/- 0.039, g/g x 100, P < 0.05), which was prevented by losartan (0.506 +/- 0.069, g/g x 100, P < 0.0001) despite similar hemodynamic load (proximal systolic pressure 146 +/- 31 vs. 136 +/- 32 mmHg, untreated vs. losartan, P = NS). Proximal systolic pressure was positively correlated with the development of ventricular hypertrophy. In the presence of AT1-receptor blockade, the increase in heart weight-to-body weight ratio at any given systolic pressure was significantly attenuated compared with untreated TAC mice. The increase in heart weight-to-body weight ratio was also significantly attenuated by captopril compared with untreated banded controls (0.542 +/- 0.091, g/g x 100, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cardiac hypertrophy associated with impaired regulation of cardiac ryanodine receptor by calmodulin and S100A1

2013 ◽  
Vol 305 (1) ◽  
pp. H86-H94 ◽  
Author(s):  
Naohiro Yamaguchi ◽  
Asima Chakraborty ◽  
Tai-Qin Huang ◽  
Le Xu ◽  
Angela C. Gomez ◽  
...  
Keyword(s):  
Body Weight ◽  
Amino Acid ◽  
Atrial Natriuretic Peptide ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Ryanodine Receptor ◽  
Weight Ratio ◽  
Heart Weight ◽  
Mrna Levels ◽  
Body Weight Ratio

The cardiac ryanodine receptor (RyR2) is inhibited by calmodulin (CaM) and S100A1. Simultaneous substitution of three amino acid residues (W3587A, L3591D, F3603A; RyR2ADA) in the CaM binding domain of RyR2 results in loss of CaM inhibition at submicromolar (diastolic) and micromolar (systolic) Ca2+, cardiac hypertrophy, and heart failure in Ryr2 ADA/ADA mice. To address whether cardiac hypertrophy results from the elimination of CaM and S100A1 inhibition at diastolic or systolic Ca2+, a mutant mouse was generated with a single RyR2 amino acid substitution (L3591D; RyR2D). Here we report that in single-channel measurements RyR2-L3591D isolated from Ryr2 D/D hearts lost CaM inhibition at diastolic Ca2+ only, whereas S100A1 regulation was eliminated at both diastolic and systolic Ca2+. In contrast to the ∼2-wk life span of Ryr2 ADA/ADA mice, Ryr2 D/D mice lived longer than 1 yr. Six-month-old Ryr2 D/D mice showed a 9% increase in heart weight-to-body weight ratio, modest changes in cardiac morphology, and a twofold increase in atrial natriuretic peptide mRNA levels compared with wild type. After 4-wk pressure overload with transverse aortic constriction, heart weight-to-body weight ratio and atrial natriuretic peptide mRNA levels increased and echocardiography showed changes in heart morphology of Ryr2 D/D mice compared with sham-operated mice. Collectively, the findings indicate that the single RyR2-L3591D mutation, which distinguishes the effects of diastolic and systolic Ca2+, alters heart size and cardiac function to a lesser extent in Ryr2 D/D mice than the triple mutation in Ryr2 ADA/ADA mice. They further suggest that CaM inhibition of RyR2 at systolic Ca2+ is important for maintaining normal cardiac function.

Abstract 13798: Ablation of the Hypertension Candidate Gene ATP2B1 Results in Increased Blood Pressure and Cardiac Hypertrophic Remodeling

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sally K Hammad ◽  
Min Zi ◽  
Sukhpal Prehar ◽  
Robert Little ◽  
Ludwig Neyses ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Diastolic Pressure ◽  
Association Studies ◽  
Weight Ratio ◽  
Blood Pressure Regulation ◽  
Heart Weight ◽  
Genome Wide Association Studies ◽  
Pressure Regulation ◽  
The Impact

Introduction: Hypertension is a major risk factor for cardiac hypertrophy and heart failure. Genome wide association studies have recently identified single nucleotide polymorphisms in ATP2B1 , the gene encoding the calcium extrusion pump, plasma membrane calcium ATPase (PMCA1), as having a strong association with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: We aim to examine whether there is a functional link between PMCA1 and blood pressure regulation, and the development of hypertension. And to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1 we generated a global PMCA1 heterozygous knockout mouse (PMCA1 Ht ). PMCA1 Ht mice had 46% to 52% reduction in PMCA1 protein expression compared to the WT, in aorta, heart, kidney and brain. To study the mice under hypertensive stress conditions, 3 month old PMCA1 Ht and wild type (WT) mice were infused via minipump with angiotensin II (1mg/Kg/daily) or water as a control. Upon angiotensin treatment, PMCA1 Ht mice showed a significantly greater increase in systolic (62.24±3.05 mmHg) and diastolic pressure (52.68±4.67 mmHg), in comparison to the WT (33.37±2.91 mmHg and 23.94±4.56 mmHg, respectively), P<0.001, n=12. Moreover, PMCA1 Ht mice showed a significantly greater hypertrophic response as indicated by a greater heart weight to tibia length ratio, cardiomyocyte cell size (410±18.7 μm 2 ), compared to WT mice (340.4±9.8 μm 2 ), and increased expression of B-type natriuretic peptide (BNP), 2.36 ± 0.25 fold change, n =5-6, P< 0.01. Echocardiography showed no significant changes between PMCA1 Ht and WT mice, in heart rate, and in cardiac function, as indicated by fractional shortening and ejection fraction. In addition, PMCA1 Ht mice showed no sign of lung congestion as indicated by lung weight to body weight ratio. Conclusion: ATP2B1 deletion leads to increased blood pressure and cardiac hypertrophy. This provides functional evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

scholarly journals Effects of long-term anti-ischemic drug treatment on Na,K-ATPase isoforms in cardiomyopathic hamsters

2021 ◽  
Vol 67 (2) ◽  
pp. 76-82
Author(s):  
Jean Michel Maixent ◽  
Sandrine V. Pierre ◽  
Stéphane Sadrin ◽  
Régis Guieu ◽  
Franck Paganelli
Keyword(s):  
Cardiac Hypertrophy ◽  
Early Stage ◽  
Weight Ratio ◽  
Body Weight Ratio ◽  
Membrane Expression ◽  
Syrian Golden Hamsters ◽  
Selective Modulation ◽  
Cardiomyopathic Hamsters ◽  
Induced Changes

We investigated the effects of long-term anti-ischemic therapy with trimetazidine on Na,K-ATPase (NKA) activity and protein expression in cardiomyopathy. NKA isoforms in membrane fractions from cardiomyopathic hamsters of the BIO 14.6 strain were studied and compared with those from healthy Syrian golden hamsters (F1B). Trimetazidine was orally administered to a subset of cardiomyopathic hamsters in the early stage of active disease (30 days) until the congestive stage (350 days). In the congestive stage of cardiac failure, the cardiomyopathic hamsters displayed altered NKA activity (-55 % vs. F1B; p<0.01), which was related to a specific decrease in abundance of the membrane NKA ?1 isoform (-27 % vs. F1B). Trimetazidine partially prevented the cardiomyopathy-induced changes in NKA activity (+38 %) and ?1 membrane expression (+ 66 %) without inducing changes in the expression of the ?2 isoform or 1 isoform of NKA. Cardiac hypertrophy and remodeling were reduced after trimetazidine treatment. Additionally, the abundance of NKA ?1 in membranes was negatively correlated with the ventricular weight/body weight ratio (an index of cardiac hypertrophy) (r2 = 0.99; p<0.0015). These findings suggest that some of the cardioprotective effect of trimetazidine during long-term cardiomyopathy may be achieved via regulation of cardiac remodeling and selective modulation cardiac NKA isoforms.

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