Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice

2010 ◽  
Vol 299 (4) ◽  
pp. H1183-H1189 ◽  
Author(s):  
Ava K. Chow ◽  
Edwin E. Daniel ◽  
Richard Schulz
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Wild Type ◽  
Stress Injury ◽  
Caveolin 1 ◽  
Myocardial Oxidative Stress

Matrix metalloproteinases (MMPs) are known to degrade components of the extracellular matrix. More recently, in myocardial oxidative stress injury including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and α-actinin. MMP activity is regulated at several levels. We recently showed that MMP-2 is localized in the caveolae of cardiomyocytes and is negatively regulated by caveolin-1 (Cav-1). The caveolin scaffolding domain of Cav-1 inhibits MMP-2 proteolytic activity in vitro, and Cav-1−/− mouse hearts have increased MMP-2 activity compared with controls. Whether this increase in MMP-2 activity translates to impaired cardiac function is unknown. Hearts isolated from Cav-1−/− mice and their wild-type controls were perfused as isolated working hearts and physiologically challenged with increasing increments of left atrial preload (7–22.5 mmHg). The hearts were then pharmacologically challenged with increasing concentrations of isoproterenol (0.1–100 nM). Functionally, the Cav-1−/− hearts were similar to the controls in heart rate, peak systolic pressure, developed pressure, and rate pressure product. At higher preload pressures, the Cav-1−/− hearts outperformed the control hearts. Coronary flow was significantly higher in Cav-1−/− hearts under all conditions. The highest concentration of isoproternol increased the heart rate of Cav-1−/− hearts more than in controls. Western blot analysis revealed no significant changes in troponin I or α-actinin between Cav-1−/− hearts and their controls. There was a significant loss of MMP-2 from both knockout and control hearts during the perfusion. In summary, despite the loss of Cav-1, Cav-1−/− hearts show similar or better cardiac function compared with wild-type hearts following physiological challenge or β-adrenergic stimulation in vitro, and this appears unrelated to changes in MMP-2.

scholarly journals Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

2013 ◽  
Vol 304 (7) ◽  
pp. H966-H982 ◽  
Author(s):  
Akihiro Masuzawa ◽  
Kendra M. Black ◽  
Christina A. Pacak ◽  
Maria Ericsson ◽  
Reanne J. Barnett ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Energy ◽  
Creatine Kinase Mb ◽  
Myocardial Energetics

Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased ( P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury.

T3 treatment does not prevent myocardial dysfunction in chronically diabetic rats

1988 ◽  
Vol 254 (2) ◽  
pp. H265-H273
Author(s):  
R. W. Barbee ◽  
R. E. Shepherd ◽  
A. H. Burns
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Cardiac Pacing ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Citrate Buffer ◽  
Heart Preparation

The isolated working heart preparation was used to investigate the effect of continuous triiodothyronine (T3) administration on cardiac function and metabolism of rats rendered diabetic for a period of 4 wk with streptozocin (STZ). T3 controlled-release pellets were implanted 1 wk after STZ (70 mg/kg) injection. Rats injected with citrate buffer without STZ received T3 pellets 1 and/or 2 wk later. A comparable number of rats received placebo pellets. Untreated diabetic rats exhibited a decrease in spontaneous heart rate and myocardial cytochrome c concentrations concurrent with depressed plasma T3 values compared with untreated controls. T3 treatment did not improve in vitro cardiac performance (assessed as cardiac output times peak systolic pressure per gram dry heart weight) in hearts from diabetic rats perfused with glucose alone. Addition of octanoate reversed this depression and improved cardiac function to a greater extent in treated than in untreated diabetic animals. However, these differences between treated and untreated diabetic animals disappeared when heart rate was controlled by cardiac pacing. Furthermore, T3 treatment of controls and diabetics did not alter the oxidation of octanoate or the cardiac responsiveness to isoproterenol. These results suggest that experimental diabetic cardiomyopathy is partly attributable to a substrate deficiency and is not due entirely to hypothyroidism.

Abstract 13879: Ischemic Postconditioning Confers Cardioprotection through Adiponectin-dependent Mitochondrial STAT3 Activation in Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Haobo Li ◽  
Michael G Irwin ◽  
Zhengyuan Xia
Keyword(s):  
Cell Injury ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Systolic Pressure ◽  
Gene Knockdown ◽  
Area At Risk ◽  
In Cells

Introduction: Signal transducer and activator of transcription 3 (STAT3) plays a key role in postconditioning (IPo) mediated protection against myocardial ischemia reperfusion injury, but the mechanism by which IPo activates STAT3 is unknown. Adiponectin (APN), a protein with anti-ischemic properties, activates STAT3. We hypothesized that IPo activates mitochondrial STAT3 (MitoSTAT3) via APN signaling. Methods and Results: Wild type (WT) and APN knockout (KO) mice were either sham operated or subjected to 30 min of coronary artery occlusion followed by 2 hours of reperfusion with or without IPo (3 cycles of 10 seconds reperfusion and 10 seconds reocclusion; n=8/group). At the end of reperfusion, KO mice exhibited more severe myocardial injury evidenced as increased infarct size (% of area at risk) 49.2±2.0 vs WT 39.4±3.5, P <0.01; plasma troponin I (ng/ml): KO 72.8±7.6 vs WT 45.7±4.0, P <0.01; worse cardiac function (lower dP/dt max and end-systolic pressure-volume relation, P <0.05); more severely impaired mitochondrial function (reductions in complex IV and complex V protein expression) and more severe reduction of MitoSTAT3 phosphorylation (activation) at site Ser727, P <0.01. IPo significantly attenuated post-ischemic cardiac injury and dysfunction with a concomitant increase in phosphorylated MitoSTAT3 and attenuation of mitochondrial dysfunction in WT (all P <0.05) but not in KO mice. In cultured cardiac H9C2 cells, hypoxic postconditioning (HPo, 3 cycles of 5 min hypoxia and 5 min reoxygenation) significantly attenuated hypoxia/reoxygenation (HR, 3 hours hypoxia/3 hours reoxygenation) induced cell injury (increased apoptotic cell death as % of HR): HR 100.2±0.4 vs HPo 78.2±4.8, P <0.05) and reduced mitochondrial transmembrane potential (% total cells, HR 37.2±4.9 vs HPo 23.5±3.7, P <0.01). APN, adiponectin receptor 1 (AdipoR1), or STAT3 gene knockdown but not AdipoR2 gene knockdown, respectively, abolished HPo cellular protection (all P <0.05 vs. HPo). APN supplementation (10μg/ml) restored HPo protection in cells with APN knockdown but not in cells with AdipoR1or STAT3 gene knockdown. Conclusion: Adiponectin and AdipoR1 signaling are required for IPo to activate myocardial mitochondrial STAT3 to confer cardioprotection.

Abstract 14391: Transient Cell Cycle Induction in Cardiomyocytes is a Promising Approach to Treat Ischemia Induced Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Riham Abouleisa ◽  
Qinghui Ou ◽  
Xian-liang Tang ◽  
Mitesh Solanki ◽  
Yiru Guo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cardiac Function ◽  
Single Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiomyocyte Proliferation ◽  
Specific Expression ◽  
Control Virus

Rationale: The regenerative capacity of the heart to repair itself after myocardial infarction (MI)is limited. Our previous study showed that ectopic introduction of Cdk1/CyclinB1 andCdk4/CyclinD1 complexes (4F) promotes cardiomyocyte proliferation in vitro and in vivo andimproves cardiac function after MI. However, its clinical application is limited due to the concernsfor tumorigenic potential in other organs. Objectives: To first, identify on a single cell transcriptomic basis the necessary reprogrammingsteps that cardiomyocytes need to undertake to progress through the proliferation processfollowing 4F overexpression, and then, to determine the pre-clinical efficacy of transient andcardiomyocyte specific expression of 4F in improving cardiac function after MI in small and largeanimals. Methods and Results: Temporal bulk and single cell RNAseq of mature hiPS-CMs treated with4F or LacZ control for 24, 48, or 72 h revealed full cell cycle reprogramming in 15% of thecardiomyocyte population which was associated with sarcomere disassembly and metabolicreprogramming. Transient overexpression of 4F specifically in cardiomyocytes was achievedusing non-integrating lentivirus (NIL) driven by TNNT2 (TNNT2-4F-NIL). One week after inductionof ischemia-reperfusion injury in rats or pigs, TNNT2-4F-NIL or control virus was injectedintramyocardially. Compared with controls, rats or pigs treated with TNNT2-4F-NIL showed a 20-30% significant improvement in ejection fraction and scar size four weeks after treatment, asassessed by echocardiography and histological analysis. Quantification of cardiomyocyteproliferation in pigs using a novel cytokinesis reporter showed that ~10% of the cardiomyocyteswithin the injection site were labelled as daughter cells following injection with TNNT2-4F-NILcompared with ~0.5% background labelling in control groups. Conclusions: We provide the first understanding of the process of forced cardiomyocyteproliferation and advanced the clinical applicability of this approach through minimization ofoncogenic potential of the cell cycle factors using a novel transient and cardiomyocyte-specificviral construct.

Abstract 61: Ablation of BK Ca Channels Results in Cardiac Hypertrophy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Harpreet Singh ◽  
Kajol Shah ◽  
Devsena Ponnalagu ◽  
Sanjay Chandrasekhar ◽  
Andrew R Kohut ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Structural Changes ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Interventricular Septum ◽  
Wild Type

Expression and activation of the large conductance calcium and voltage-gated potassium (BK Ca ) channels encoded by Kcnma1 gene is shown to be vital in cardioprotection from ischemia-reperfusion injury. BK Ca channels present in SA node cells regulate the heart rate, and in blood vessels play an active role in vascular relaxation. However, the role of BK Ca in regulation of structure and function of the heart is not fully-established. Using Kcnma1 -/- mice, we have observed structural changes in cardiomyocytes and compromised cardiac function as compared to wild type mice. Absence of BK Ca resulted in significant increase in size of adult cardiomyocytes (from 7.95 + 0.1 um 2 to 9.68 + 0.1 um 2 , p < 0.01, n=480 cells each) and also increased cardiac fibrosis. Further to determine underlying signaling mechanisms in cardiac hypertrophy, we performed microarray analysis of RNAs isolated from wild type and Kcnma1 -/- mice (n=3) hearts. We found up regulation of a class of cardiac hypertrophy markers (myosin variants) and changes in the expression of several mitochondrial genes (such as ND4) directly associated with heart diseases in Kcnma1 -/- mice. To evaluate the functional consequence of absence of BK Ca , we performed high-resolution echocardiography on wild type and Kcnma1 -/- mice. Under anesthesia (1.5% isoflurane), left ventricle of Kcnma1 -/- mice showed significant reduction (p < 0.05) in ejection fraction (56 + 2 %, n=7) as compared to wild type (74 + 3 %, n=6) as well as fractional shortening (23 + 3 %, n=7, and 39 + 3 %, n=6, respectively). Similarly, right ventricle had a lower ejection fraction (35.7 + 4% vs 56.9 + 5 %, n > 5) in Kcnma1 -/- as compared to wild type mice. In agreement with our histopathology and microarray data, Kcnma1 -/- mice showed increased posterior wall thickness (0.75 + 0.3 mm vs 0.62 + 0.1 mm) and interventricular septum thickness (0.83 + 0.4 mm, n=7 vs 0.68 + 0.3 mm, n=6) . Together, these data imply that BK Ca plays a direct role in cardiac hypertrophy and cardiac function.

Abstract 552: Bradykinin Receptor B1/ Matrix Metalloprotease 3 Pathway is a Novel Target in Preventing Cardiac Ischemia-reperfusion Injury

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Qin Zhang ◽  
Lizhuo Ai ◽  
Lifeng Liu ◽  
Cristian Betancourt ◽  
Maura Knapp ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Endothelial Barrier ◽  
Matrix Metalloprotease ◽  
Barrier Dysfunction ◽  
Area At Risk ◽  
Bradykinin Receptor

Introduction: Impaired endothelial function leads to the progression of heart failure after Ischemia-reperfusion (IR). Kinin activation of bradykinin receptor 1 (B1R), a G protein-coupled receptor that has been found to induce capillary leakage, may serve as a critical mediator in cardiac microvascular barrier dysfunction. However, the underlying mechanisms are not clear. We found that B1R inhibition abolished IR-induced endothelial matrix metalloprotease (MMP3) expression and improved endothelial barrier formation. Thus, we hypothesized that B1R antagonist protects against cardiac IR injury through an MMP3 pathway. Methods and Results: MMP3-/- mice and their littermate controls (WT) were subjected to either cardiac IR or sham control. The baseline characteristics of these mice showed minimal phenotypes. Cardiac function was determined at 3, 7 and 24 days post-IR by echocardiography. The MMP3-/- mice displayed improved cardiac function compared to the control mice, as determined by fractional shortening (26% ± 1.1 MMP3-/- vs. 21% ± 0.9 WT, p<0.05, n=5) and ejection fraction (48% ± 1.9 MMP3-/- vs. 42% ± 2.8.1 WT, p<0.05, n=5), and treating with B1R antagonist (300 μg/Kg) significantly reduced serum MMP3 levels (p<0.01). Compared to the control mice, MMP3-/- mice had significantly less infarction/area at risk 24 hours post-IR demonstrated through TTC staining. In vitro studies revealed that cellular hypoxia-reoxygenation (HR) injury significantly increased both B1R and MMP3 expression levels in primary isolated cardiac mice microvascular endothelial cells (mCMVEC). MMP3 levels were measured via ELISA. Moreover, B1R agonist treatment (1uM) increased MMP3 levels, while the use of the antagonist attenuated the increase of MMP3 in response to HR. Finally, the use of B1R antagonist improved MMP3 induced endothelial barrier dysfunction, which was measured by the electric cell-substrate impedance sensing (ECIS) system. Taken together, the results demonstrated that B1R antagonist abolished IR induced MMP3 induction and that the deletion of MMP3 is protective of cardiac function upon IR injury. Conclusions: MMP3 is a critical regulator of cardiac microvascular barrier function, and B1R/MMP3 could potentially serve as a novel therapeutic target for heart failure in response to IR injury.

scholarly journals Enhanced gene expression of Na+/Ca2+exchanger attenuates ischemic and hypoxic contractile dysfunction

2000 ◽  
Vol 279 (6) ◽  
pp. H2846-H2854 ◽  
Author(s):  
Thomas G. Hampton ◽  
Ju-Feng Wang ◽  
Joseph DeAngelis ◽  
Ivo Amende ◽  
Kenneth D. Philipson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Intracellular Calcium ◽  
Systolic Pressure ◽  
Contractile Dysfunction ◽  
Compensatory Mechanism ◽  
Wild Type ◽  
Generating Capacity ◽  
And Function

Enhanced gene expression of the Na+/Ca2+exchanger in failing hearts may be a compensatory mechanism to promote influx and efflux of Ca2+, despite impairment of the sarcoplasmic reticulum (SR). To explore this, we monitored intracellular calcium (Cai 2+) and cardiac function in mouse hearts engineered to overexpress the Na+/Ca2+ exchanger and subjected to ischemia and hypoxia, conditions known to impair SR Cai 2+transport and contractility. Although baseline Cai 2+and function were similar between transgenic and wild-type hearts, significant differences were observed during ischemia and hypoxia. During early ischemia, Cai 2+ was preserved in transgenic hearts but significantly altered in wild-type hearts. Transgenic hearts maintained 40% of pressure-generating capacity during early ischemia, whereas wild-type hearts maintained only 25% ( P < 0.01). During hypoxia, neither peak nor diastolic Cai 2+ decreased in transgenic hearts. In contrast, both peak and diastolic Cai 2+ decreased significantly in wild-type hearts. The decline of Cai 2+ was abbreviated in hypoxic transgenic hearts but prolonged in wild-type hearts. Peak systolic pressure decreased by nearly 10% in hypoxic transgenic hearts and >25% in wild-type hearts ( P < 0.001). These data demonstrate that enhanced gene expression of the Na+/Ca2+ exchanger preserves Cai 2+ homeostasis during ischemia and hypoxia, thereby preserving cardiac function in the acutely failing heart.

Effect of altered thyroid status on in vitro cardiac performance in rats

1987 ◽  
Vol 252 (4) ◽  
pp. H788-H795 ◽  
Author(s):  
K. H. McDonough ◽  
V. Chen ◽  
J. J. Spitzer
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Cardiac Output ◽  
Thyroid Hormone ◽  
Systolic Pressure ◽  
Heart Weight ◽  
The Difference ◽  
Altered Thyroid ◽  
Similar Body

Effect of a chronic excess or deficit of thyroid hormone on intrinsic myocardial performance in rats was assessed. Animals were thyroidectomized or treated with thyroid hormone or vehicle 6-7 wk before the study. Body weight and heart weight were decreased in the hypothyroid group, and heart weight was elevated in the hyperthyroid group. Hearts were removed from thyroidectomized, euthyroid or thyroid-treated animals and studied as isolated, perfused working heart preparations. Ventricular function curves were generated by increasing left atrial filling pressure, whereas outflow resistance was not varied. Coronary flow, aortic outflow (and thus cardiac output), heart rate, and peak aortic systolic pressure were measured as a function of preload. These studies showed that performance of hearts from hyperthyroid animals was similar to that of euthyroid controls. Hearts from hypothyroid rats had decreased rate, pressure, and cardiac output but normal stroke volume. Since heart weight was 55% lower than control, normalization of volume work to dry heart weight reversed the difference in cardiac output. Comparison of hearts from hypothyroid animals to control rats of similar weight showed minimal differences in pump function. Thus hyperthyroidism did not result in altered in vitro cardiac output or peak systolic pressure as a function of changing preload when compared with age-matched euthyroid controls, hypothyroidism resulted in a decreased in vitro heart rate but greater cardiac output normalized to heart weight when compared with age-matched controls and hyperthyroid animals; external pacing of hypothyroid hearts yielded myocardial work parameters that were comparable to euthyroid control rats of similar body weight; and cardiac efficiency was significantly greater in hypothyroid hearts than in hyperthyroid hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts

2002 ◽  
Vol 283 (4) ◽  
pp. H1562-H1568 ◽  
Author(s):  
Heather R. Cross ◽  
Elizabeth Murphy ◽  
Richard G. Black ◽  
John Auchampach ◽  
Charles Steenbergen
Keyword(s):  
Heart Rate ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Wild Type ◽  
Basal Heart Rate ◽  
Developed Pressure

To determine whether A3 adenosine receptor (A3AR) signaling modulates myocardial function, energetics, and cardioprotection, hearts from wild-type and A3AR-overexpressor mice were subjected to 20-min ischemia and 40-min reperfusion while 31P NMR spectra were acquired. Basal heart rate and left ventricular developed pressure (LVDP) were lower in A3AR-overexpressor hearts than wild-type hearts. Ischemic ATP depletion was delayed and postischemic recoveries of contractile function, ATP, and phosphocreatine were greater in A3AR-hearts. To determine the role of depressed heart rate and to confirm A3AR-specific signaling, hearts were paced at 480 beats/min with or without 60 nmol/l MRS-1220 (A3AR-specific inhibitor) and then subjected to ischemia-reperfusion. LVDP was similar in paced A3AR-overexpressor and paced wild-type hearts. Differences in ischemic ATP depletion and postischemic contractile and energetic dysfunction remained in paced A3AR-overexpressor hearts versus paced wild-type hearts but were abolished by MRS-1220. In summary, A3AR overexpression decreased basal heart rate and contractility, preserved ischemic ATP, and decreased postischemic dysfunction. Pacing abolished the decreased contractility but not the ATP preservation or cardioprotection. Therefore, A3AR overexpression results in cardioprotection via a specific A3AR effect, possibly involving preservation of ATP during ischemia.

scholarly journals STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

2013 ◽  
Vol 305 (4) ◽  
pp. H446-H458 ◽  
Author(s):  
Helen E. Collins ◽  
Xiaoyuan Zhu-Mauldin ◽  
Richard B. Marchase ◽  
John C. Chatham
Keyword(s):  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Molecular Regulation ◽  
Cardiomyocyte Hypertrophy ◽  
Substantial Evidence ◽  
Contraction Coupling

Store-operated Ca2+ entry (SOCE) is critical for Ca2+ signaling in nonexcitable cells; however, its role in the regulation of cardiomyocyte Ca2+ homeostasis has only recently been investigated. The increased understanding of the role of stromal interaction molecule 1 (STIM1) in regulating SOCE combined with recent studies demonstrating the presence of STIM1 in cardiomyocytes provides support that this pathway co-exists in the heart with the more widely recognized Ca2+ handling pathways associated with excitation-contraction coupling. There is now substantial evidence that STIM1-mediated SOCE plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo, and there is growing support for the contribution of SOCE to Ca2+ overload associated with ischemia/reperfusion injury. Here, we provide an overview of our current understanding of the molecular regulation of SOCE and discuss the evidence supporting the role of STIM1/Orai1-mediated SOCE in regulating cardiomyocyte function.

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