Effects of sarcoplasmic reticulum Ca<sup>2+</sup>-ATPase overexpression in postinfarction rat myocytes

Ahlers, Belinda A.; Song, Jianliang; Wang, JuFang; Zhang, Xue Qian; Carl, Lois L.; Tadros, George; Rothblum, Lawrence I.; Cheung, Joseph Y.

doi:10.1152/japplphysiol.00013.2005

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…By contrast, the persistent decrease in left ventricular −dP/dt and elevated LVEDP in AMD3100-treated post-MI rats suggests that cellular events implicated in relaxation remain dysfunctional. Calcium uptake by SERCA2 plays an integral role in ventricular relaxation and decreased protein expression, and activity was reported in cardiac myocytes isolated from 3-week post-MI rats [1,21,31]. Although protein content and activity were not measured in the present study, the persistent downregulation of SERCA2 mRNA in AMD3100-treated post-MI rats indirectly provides a plausible mechanism contributing to impaired relaxation.…”

Section: Discussionmentioning

confidence: 53%

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Proulx

El-Helou

Gosselin

et al. 2007

Pflugers Arch - Eur J Physiol

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To examine the biological impact of locally expressed stromal cell-derived factor-1alpha (SDF-1alpha) during the acute phase of remodeling after myocardial infarction (MI), rats were treated with the selective CXCR4 receptor antagonist AMD3100 (1 mg/kg; given 24 h post-MI and continued for 6 days). In 1-week post-MI rats, intense SDF-1 immunoreactivity was detected in scar-residing vessels, and SDF-1alpha messenger ribonucleic acid (mRNA) levels were significantly greater in the infarct region compared to the noninfarcted left ventricle (NILV). AMD3100 treatment of post-MI rats reduced infarct size, improved systolic function, and partially suppressed the increased expression of atrial natriuretic peptide mRNA in the NILV. The latter finding indirectly suggests that SDF-1alpha may have contributed to the hypertrophic response of the NILV. SDF-1alpha treatment of neonatal rat ventricular myocytes (NNVMs) failed to promote protein synthesis. However, in hypertrophied NNVMs, SDF-1alpha treatment further augmented (3)H-leucine uptake, and AMD3100 selectively inhibited the increase in protein synthesis. Collectively, these data support the existence of an SDF-1alpha gradient in the damaged rat myocardium increasing toward the infarct region and highlight the novel observation that AMD3100 antagonism of the SDF-1alpha/CXCR4 axis reduced scar expansion and improved contractility. In vitro data further suggest that SDF-1alpha may have contributed to the hypertrophic response of the NILV.

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Section: Discussionmentioning

confidence: 53%

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Proulx

El-Helou

Gosselin

et al. 2007

Pflugers Arch - Eur J Physiol

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“…Normal intracellular Ca 2+ handling in cardiomyocytes is maintained by multiple proteins, including L-type Ca 2+ channels, NCX, RyR2 and Ca 2+ -ATPase. 22,23 In the present study, we investigated whether choline affected calcium stores and found that the inhibitory effect of choline on [Ca 2+ ] i overload is not mediated by RyRs. Fig.…”

Section: Discussionmentioning

confidence: 88%

Activation of cardiac M₃ muscarinic acetylcholine receptors has cardioprotective effects against ischaemia‐induced arrhythmias

Wang

Han

Jiang

et al. 2012

Clin Exp Pharma Physio

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Increasing evidence indicates the important roles of M(3) muscarinic acetylcholine receptors (M(3) mAChR) in the regulation and maintenance of cardiac function and heart disease. In the present study, we investigated whether the M(3) mAChR mediates the cardioprotection against ischaemia-induced arrhythmias and the mechanisms involved. Myocardial ischaemia was established in Wistar rats by occlusion of the left anterior descending coronary artery. Rats were treated with choline chloride (an M(3) mAChR agonist; 10 mg/kg, i.v.) 10 min before occlusion. In addition, 4-diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP; 0.12 μg/kg, i.v.) was administered 5 min before choline in the 4-DAMP-treated group. Ischaemia-induced arrhythmias were evaluated in each group for a period of 1 h after occlusion. After 24 h occlusion, protein and mRNA levels of L-type Ca(2+) channels and the Na(+) /Ca(2+) exchanger (NCX) were determined. Ischaemia-induced arrhythmias following coronary artery occlusion were diminished by choline and this effect was reversed in the 4-DAMP-treated group. In vitro, the effects of myocardial ischaemia were simulated by incubating isolated ventricular cardiomyocytes with Tyrode's solution (pH 6.8). Intracellular Ca(2+) overload was confirmed and this was decreased by choline. Furthermore, choline reduced the L-type Ca(2+) current (I(C) (a,) (L) ) compared with cardiomyocytes incubated in Tyrode's solution (pH 6.8) alone. Choline reduced the 'ischaemia'-induced upregulated expression of L-type Ca(2+) channels and NCX at both the protein and mRNA level. Based on these results, choline has an obvious protective effect against ischaemia-induced arrhythmias that is mediated via activation of cardiac M(3) mAChR, which reduces Ca(2+) overload mediated by L-type Ca(2+) channels and the NCX.

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“…In myocardial infarction and human heart failure, there is a decrease in the expression of serca2a which is hallmark of cardiac myocyte dysfunction [40–43]. Studies depict that decrease in the expression of serca2a leads to decrease in contractility in rats after MI and increase in the expression of serca2a can lead to augmented contractility in cardiovascular diseases [44,45]. Ryanodine receptor in the sarcoplasmic reticulum works in conjunction with the serca2a and helps maintaining calcium levels by calcium efflux [46].…”

Section: Discussionmentioning

confidence: 99%

Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy

Chaturvedi

Kalani

Familtseva

et al. 2015

International Journal of Cardiology

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Background TIMP4 (Tissue Inhibitors of Matrix Metalloprotease 4), goes down in failing hearts and mice lacking TIMP4 show poor regeneration capacity after myocardial infarction (MI). This study is based on our previous observation that administration of cardiac inhibitor of metalloproteinase (~TIMP4) attenuates oxidative stress and remodeling in failing hearts. Therefore, we hypothesize that TIMP4 helps in cardiac regeneration by augmenting contractility and inducing the differentiation of cardiac progenitor cells into cardiomyocytes. Methods To validate this hypothesis, we transfected mouse cardiomyocytes with TIMP4 and TIMP4-siRNA and performed contractility studies in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. We evaluated the calcium channel gene serca2a (sarcoplasmic reticulum calcium ATPase2a) and mir122a which tightly regulates serca2a to explain the changes in contractility. We treated mouse embryonic stem cells with cardiac extract and cardiac extract minus TIMP4 (using TIMP4 monoclonal antibody) to examine the effect of TIMP4 on differentiation of cardiac progenitor cells. Results Contractility was augmented in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. There was elevated expression of serca2a in the TIMP4 transformed myocytes and down regulation of mir122a. The cells treated with cardiac extract containing TIMP4 showed cardiac phenotype in terms of Ckit+, GATA4+ and Nkx2.5 expression. Conclusion This is a novel report suggesting that TIMP4 augments contractility and induces differentiation of progenitor cells into cardiac phenotype. In view of the failure of MMP9 inhibitors for cardiac therapy, TIMP4 provides an alternative approach, being an indigenous molecule and a natural inhibitor of MMP9.

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Effects of sarcoplasmic reticulum Ca²⁺-ATPase overexpression in postinfarction rat myocytes

Cited by 11 publications

References 38 publications

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Activation of cardiac M₃ muscarinic acetylcholine receptors has cardioprotective effects against ischaemia‐induced arrhythmias

Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy

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Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes

Cited by 11 publications

References 38 publications

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

Activation of cardiac M3 muscarinic acetylcholine receptors has cardioprotective effects against ischaemia‐induced arrhythmias

Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy

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Effects of sarcoplasmic reticulum Ca²⁺-ATPase overexpression in postinfarction rat myocytes

Activation of cardiac M₃ muscarinic acetylcholine receptors has cardioprotective effects against ischaemia‐induced arrhythmias