Controlling Cardiomyocyte Survival

2008 ◽  
pp. 41-57 ◽  
Author(s):  
Nicolaas de Jonge ◽  
Marie Jose Goumans ◽  
Daan Lips ◽  
Rutger Hassink ◽  
Eva J. Vlug ◽  
...  
Keyword(s):  
Cardiomyocyte Survival

Gαq expression activates EGFR and induces Akt mediated cardiomyocyte survival: dissociation from Gαq mediated hypertrophy

2006 ◽  
Vol 40 (5) ◽  
pp. 597-604 ◽  
Author(s):  
Amy L. Howes ◽  
Shigeki Miyamoto ◽  
John W. Adams ◽  
Elizabeth A. Woodcock ◽  
Joan Heller Brown
Keyword(s):  
Cardiomyocyte Survival

Abstract O-3: A β1-Adrenergic Receptor/β-Arrestin1-Regulatable MicroRNA, MiR-150 Protects the Mouse Heart from Ischemic Injury by Repressing Pro-apoptotic Egr2 and P2x7r

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Il-man Kim ◽  
Yaoping Tang ◽  
Yongchao Wang ◽  
Kyoung-mi Park ◽  
Qiuping Hu
Keyword(s):  
Adrenergic Receptor ◽  
Cardiac Injury ◽  
Ischemic Injury ◽  
Mouse Heart ◽  
Functional Remodeling ◽  
Β Blocker ◽  
Genetic Deletion ◽  
Circulating Levels ◽  
Cardiomyocyte Survival

MicroRNA (miR)-150 is down-regulated in patients with acute myocardial infarction (AMI), atrial fibrillation, dilated and ischemic cardiomyopathy as well as in various mouse heart failure (HF) models. Circulating miR-150 has been recently proposed as a better biomarker of HF than clinically used markers such as brain natriuretic peptide. We recently showed that β-arrestin1-biased β1-adrenergic receptor (β1AR) cardioprotective signaling activated by the β-arrestin-biased β-blocker, carvedilol (Carv) stimulates the processing of miR-150 in the heart (see figure A). However, the potential role of miR-150 in ischemic injury and HF is unknown. Here, we show that genetic deletion of miR-150 in mice causes abnormalities in cardiac structural and functional remodeling after MI. The cardioprotective roles of miR-150 during ischemic injury were attributed to repression of the pro-apoptotic genes egr2 (zinc binding transcription factor induced by ischemia) and p2x7r (pro-inflammatory ATP receptor) [see figure B]. These findings reveal a pivotal role for miR-150 as a regulator of cardiomyocyte survival during cardiac injury. In conclusion, our study will help to stratify HF patients that may respond better to β-arrestin-biased β-blockers, which is guided by circulating levels of miR-150.

Abstract P336: Endogenous Alpha-1a Adrenergic Receptors Promote Cardiomyocyte Survival Through Suppression Of Rip Kinase-mediated Necroptosis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jiandong Zhang ◽  
Peyton Sandroni ◽  
Wei Huang ◽  
Brian C Jensen
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Hmgb1 Level ◽  
Programmed Necrosis ◽  
Apoptosis Markers ◽  
Kinase Pathway ◽  
Cardiomyocyte Survival ◽  
Serum Hmgb1 Level

Our previous work has demonstrated essential protective roles for the endogenous cardiomyocyte alpha-1A adrenergic receptor (α1A-AR) subtype in mouse models of heart failure. However, the underlying mechanism of this protective phenotype is unclear. To address this gap in knowledge, we bred a mouse line lacking α1A-ARs on cardiomyocytes by crossing αMHC-cre mice with floxed α1A mice (CMKO= cre+ fl/fl, CMWT= cre- fl/fl), and subjected males to permanent LAD ligation. CMKO mice had increased serum HMGB1 level, larger infarcts and higher mortality. We found that RIP1/3-mediated programmed necrosis (necroptosis), but not apoptosis was exaggerated in CMKO mice 3 days after ligation. We then tested whether RIP1 inhibition with Nec-1s could mitigate this injury. Mice were given Nec-1s (1.65 mg/kg) or vehicle 10 mins prior to LAD ligation, followed by daily IV injection. Nec-1s treatment diminished post-ligation RIP1 (0.62±0.02 vs. 0.78±0.23 A.U., p=NS) and RIP3 expression (0.33±0.1 vs. 0.26±0.10 A.U., p=NS) in CMWT and CMKO mice respectively. Serum level of HMGB1 on D3 was markedly reduced in both CMWT (45.1%) and CMKO (61.1 %) after Nec-1s treatment. There was no difference between Nec-1s treated CMWT and CMKO mice (147±53 vs. 174±37 pg/mL, p=NS), indicating that blocking the RIP kinase pathway abrogates the exaggerated cell death in CMKO mice after ligation. Likewise, Nec-1s-treated CMKO mice had similar infarct areas to CMWT controls (16.2±4.5 vs. 19.9±4.6%, p=NS), further confirming that targeting necroptosis abrogates pathological damage. Collectively these Nec-1s data suggest that RIP-mediated necroptosis may account for larger infarcts in CMKO mice. Interestingly, expression of the apoptosis markers c-caspase-3 and PARP was similar between CMWT and CMKO mice, suggesting that the α1A-AR specifically regulates necroptosis. In sum, our data demonstrate that RIP kinase-mediated necroptosis contributes to susceptibility to injury in mice lacking cardiomyocyte α1A-ARs.

In Situ Gelling Scaffolds Loaded with Platelet Growth Factors to Improve Cardiomyocyte Survival after Ischemia

2018 ◽  
Vol 5 (1) ◽  
pp. 329-338 ◽  
Author(s):  
Francesca Saporito ◽  
Lauren M. Baugh ◽  
Silvia Rossi ◽  
Maria Cristina Bonferoni ◽  
Cesare Perotti ◽  
...  
Keyword(s):  
Growth Factors ◽  
In Situ Gelling ◽  
Cardiomyocyte Survival

scholarly journals Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 are linked to cardiomyocyte survival following oxygen and substrate deprivation

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Matthias Johannes Merkel ◽  
Lijuan Liu ◽  
Zhiping Cao ◽  
William Packwood ◽  
Ines P. Koerner ◽  
...  
Keyword(s):  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Substrate Deprivation ◽  
Cardiomyocyte Survival

scholarly journals Chronic Heart Rate Reduction Facilitates Cardiomyocyte Survival After Myocardial Infarction

2010 ◽  
Vol 293 (5) ◽  
pp. 839-848 ◽  
Author(s):  
Rong-Lin Zhang ◽  
Lance P. Christensen ◽  
Robert J. Tomanek
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Heart Rate Reduction ◽  
Rate Reduction ◽  
Cardiomyocyte Survival

Abstract 3474: Cardiac -Specific SOCS3 Dificient Mice Shows Resistance to Lipopolysaccharide-Induced Cardiac Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Futamata Nobuyoshi ◽  
Hldeo Yasukawa ◽  
Toyoharu Ohba ◽  
Kazutoshi Mawatari ◽  
Daisuke Fukui ◽  
...  
Keyword(s):  
Western Blot ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Left Ventricular Ejection ◽  
Cytokine Signaling ◽  
Rt Pcr ◽  
Lv Dysfunction ◽  
Stat3 Signaling ◽  
Cardiomyocyte Survival

Background : Lypopolysaccharide (LPS)-induced left ventricular (LV) dysfunction is a well-established model for sepsis-induced acute heart failure. STAT3 signaling in the heart has been shown to promote cardiomyocyte survival during LPS-induced LV dysfunction. Little is known, however, about the role of negative regulation of STAT3 signaling during LPS-induced LV dysfunction. Suppressor of cytokine signaling 3 (SOCS3) is an intrinsic negative regulator of gp130 cytokine-induced STAT3 signaling that plays an important role in cardiomyocyte survival. In this study, we determined whether STAT3 signaling and its negative regulator SOCS3 would play a role in LPS-induced LV dysfunction. Methods and Results : We examined the activation of STAT3 and inductions of gp130 cytokines and SOCS3 in the wild-type (WT) mice hearts after LPS injection by western blot and real-time PCR (RT-PCR). RT-PCR revealed that gp130 cytokines were markedly increased after AMI. Western blot revealed that STAT3 was markedly phosphorylated and SOCS3 was induced in WT mice hearts after LPS injection. To investigate the role of STAT3 signaling and SOCS3 in LPS-induced LV dysfunction, we generated cardiac-specific SOCS3 knockout mice (SOCS3-CKO). Left ventricular ejection fraction (LVEF) of SOCS3-CKO mice was similar to that of WT mice at baseline (64.2 ± 6.1 vs. 62.4 ± 4.4%). LPS (30mg/kg) elicited a significant and robust reduction of LVEF in both SOCS3-CKO mice and WT mice 3 hr after LPS injection (18 ± 4.5 vs. 16 ± 5.2%, p <0.01). LVEF in WT mice was further reduced 6 hr after LPS injection. On the other hand, interestingly, LVEF was restored to the baseline in SOCS3-CKO mice 6 hr after LPS injection (10.4 ± 3.9 vs. 62.2 ± 8.1%, p <0.01). Also the duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Furthermore, SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection ( p <0.01). Conclusion : Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice, possibly by augmenting the STAT3-mediated gp130 cytokine signaling.

Abstract 79: Sarcospan Has a Protective Effect During Development of Cardiac Disease

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Michelle S Parvatiyar ◽  
Reginald T Nguyen ◽  
Maria C Jordan ◽  
Kenneth P Roos ◽  
Rachelle H Crosbie-Watson
Keyword(s):  
Cell Adhesion ◽  
Cardiac Tissue ◽  
Physiological Function ◽  
Wall Stress ◽  
Muscle Dysfunction ◽  
Wild Type ◽  
Aortic Constriction ◽  
Muscle Histology ◽  
Cardiomyocyte Survival ◽  
Laminin Binding

Sarcospan (SSPN) has an important role in stabilizing sarcolemmal dystrophin- and utrophin-glycoprotein adhesion complexes at the cell membrane. Loss of cell adhesion leads to contraction-induced muscle damage, causing muscle dysfunction and cell death. Recently we have shown a specific role for SSPN in modulating cardiac cell adhesion and physiological function. After transthoracic aortic constriction (TAC), SSPN-null mice transitioned toward failure faster than wild-type (WT) mice. Muscle histology revealed large focal areas of collagen deposition in SSPN-null hearts after TAC compared to WT hearts, suggesting that increased membrane fragility affected cardiomyocyte survival. Our laboratory has shown that SSPN loss reduces sarcolemmal dystrophin levels and associated adhesion complexes in the heart. Whereas, the complete loss of dystrophin leads to development of Duchenne muscular dystrophy (DMD), causing cardiac dysfunction and early mortality. Overexpression of SSPN in DMD mice increased cell adhesion and laminin binding in hearts, leading to improvements in tissue histopathology and increased expression of utrophin, a functional homologue of dystrophin. Examining the restorative potential of SSPN in dystrophic cardiac tissue, led us to query whether compensatory upregulation of SSPN occurs in failing hearts of TAC-treated WT mice. In failing non-DMD hearts, we found that SSPN expression is increased. We have evidence of a chaperone role for SSPN, and its increased expression in the failing heart may contribute to the increased localization of dystrophin and associated glycoprotein complexes at the sarcolemma, which we observed in failing WT hearts compared to untreated controls. The upregulation of cell-stabilizing cell adhesion complexes may compensate for increased wall stress and counter pathological processes that culminate in cardiomyocyte demise, and we are exploring whether naturally increased expression or transgenic overexpression of SSPN in the heart may protect against damage. In summary, we have found that SSPN promotes cardiac function by maintaining cell adhesion and promoting cell survival during disease conditions.

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