Abstract P409: GSK-3β Deficiency In Cardiomyocyte Induces Cardiac Progenitor Cell Proliferation In The Ischemic Heart

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Ayesha Yusuf ◽  
Rizwan Qaisar ◽  
James R Woodgett ◽  
Firdos Ahmad
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Stem Cell Marker ◽  
Cardiomyocyte Proliferation ◽  
Littermate Control ◽  
Gsk 3Β ◽  
Immunofluorescence Labeling

The cardiomyocytes are terminally differentiated cells and ischemia-induced cardiomyopathy is an irreparable loss. Novel strategies are needed to induce resident cardiac progenitor cells (CPCs) proliferation in situ to enhance the possibility of cardiac regeneration. Here we sought to identify a potential role for glycogen synthase kinase-3β (GSK-3β), a critical regulator of cell proliferation and differentiation, in CPCs proliferation in the ischemic heart. Cardiomyocyte-specific conditional GSK-3β knockout (cKO) and littermate control mice were recruited and challenged with myocardial infarction (MI). The cardiac function was assessed using trans-thoracic M-mode echocardiography. The level of CPC proliferation in the ischemic cKO hearts was determined at 2, 4 and 8 weeks post-MI through immunofluorescence labeling of stem cell marker c-Kit. To confirm the lineage of identified c-Kit -positive cells (KPCs) in the heart, a hematopoietic lineage marker was stained along with c-Kit. The cardiac left ventricular chamber dimension (LVID) and contractile functions were comparable until 2 weeks post-MI. The cKO mice displayed significantly preserved LV chamber [LVIDd(mm); 5.01±0.67 vs.6.09±0.65, p =0.01] and contractile function [LVEF(%); 31.98±8.52 vs. 18.06±7.11., p =0.01] in comparison to control mice at 4 week post-MI. Consistent with protective phenotypes, an increased percentage of KPC was observed in the cKO hearts at 4 and 6-weeks post-MI which was accompanied by an increased level of cardiomyocyte proliferation. Further analysis revealed that the observed increased number of KPCs in the ischemic cKO hearts were mostly from a cardiac lineage as the majority of identified KPCs were negative for the hematopoietic marker, CD45. In conclusion, our findings strongly suggest that GSK-3β inhibits CPCc proliferation post-ischemia, and loss of GSK-3β in cardiomyocytes promotes resident CPCc proliferation potentially through paracrine mechanisms.

scholarly journals Cardiomyocyte GSK-3β deficiency induces cardiac progenitor cell proliferation in the ischemic heart through paracrine mechanisms

2021 ◽  
Author(s):  
Ayesha M. Yusuf ◽  
Rizwan Qaisar ◽  
Abaher O. Al-Tamimi ◽  
Manju Nidagodu Jayakumar ◽  
James Robert Woodgett ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factors ◽  
Progenitor Cell ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Cardiac Regeneration ◽  
Left Ventricular ◽  
Cardiac Progenitor Cell ◽  
Gsk 3Β

Cardiomyopathy is an irreparable loss and novel strategies are needed to induce resident cardiac progenitor cell (CPC) proliferation in situ to enhance the possibility of cardiac regeneration. Here we identify a potential role for glycogen synthase kinase-3β (GSK-3β), a critical regulator of cell proliferation and differentiation, in CPC proliferation that occurs after myocardial infarction (MI). Cardiomyocyte-specific conditional GSK-3β knockout (cKO) and littermate control mice were employed and challenged with MI. Though cardiac left ventricular chamber dimension (LVID) and contractile functions were comparable at two week post-MI, cKO mice displayed significantly preserved LV chamber and contractile function vs. control mice at four-weeks post-MI. Consistent with protective phenotypes, an increased percentage of c-kit positive cells (KPCs) were observed in the cKO hearts at four and six weeks post-MI which was accompanied by increased levels of cardiomyocyte proliferation. Further analysis revealed that the observed increased number of KPCs in the ischemic cKO hearts was mainly from a cardiac lineage as the majority of identified KPCs were negative for the hematopoietic marker, CD45. Mechanistically, cardiomyocyte-GSK-3β profoundly suppresses the expression of growth factors (GFs), including basic-FGF angiopoietin-2, erythropoietin, stem cell factor (SCF), PDGF-BB, G-CSF, and VEGF, post-hypoxia. In conclusion, our findings strongly suggest that loss of cardiomyocyte-GSK-3β promotes cardiomyocyte and resident CPC proliferation post-MI. The induction of cardiomyocytes and CPC proliferation in the ischemic cKO hearts is potentially regulated by autocrine and paracrine signaling governed by dysregulated growth factors post-MI. A strategy to inhibit cardiomyocyte GSK-3β could be helpful for promotion of in-situ cardiac regeneration post-MI injury.

Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac dysfunction and decreased survival only in males

2007 ◽  
Vol 292 (2) ◽  
pp. H838-H845 ◽  
Author(s):  
Stephen W. Luckey ◽  
Jason Mansoori ◽  
Kelly Fair ◽  
Christopher L. Antos ◽  
Eric N. Olson ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Mouse Model ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Premature Death ◽  
Contractile Dysfunction ◽  
Sexually Dimorphic ◽  
Cardiac Growth ◽  
Hypertrophic Growth ◽  
Gsk 3Β

Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy (HCM) that is characterized by hypertrophy, histopathology, contractile dysfunction, and sudden death. The signaling pathways involved in the pathology of HCM have not been elucidated, and an unresolved question is whether blocking hypertrophic growth in HCM may be maladaptive or beneficial. To address these questions, a mouse model of HCM was crossed with an antihypertrophic mouse model of constitutive activated glycogen synthase kinase-3β (caGSK-3β). Active GSK-3β blocked cardiac hypertrophy in both male and female HCM mice. However, doubly transgenic males (HCM/GSK-3β) demonstrated depressed contractile function, reduced sarcoplasmic (endo) reticulum Ca2+-ATPase (SERCA) expression, elevated atrial natriuretic factor (ANF) expression, and premature death. In contrast, female HCM/GSK-3β double transgenic mice exhibited similar cardiac histology, function, and survival to their female HCM littermates. Remarkably, dietary modification from a soy-based diet to a casein-based diet significantly improved survival in HCM/GSK-3β males. These findings indicate that activation of GSK-3β is sufficient to limit cardiac growth in this HCM model and the consequence of caGSK-3β was sexually dimorphic. Furthermore, these results show that blocking hypertrophy by active GSK-3β in this HCM model is not therapeutic.

scholarly journals GSK-3β heterozygous knockout is cardioprotective in a knockin mouse model of familial dilated cardiomyopathy

2016 ◽  
Vol 310 (11) ◽  
pp. H1808-H1815 ◽  
Author(s):  
Rasha M. S. M. Mohamed ◽  
Sachio Morimoto ◽  
Islam A. A. E.-H. Ibrahim ◽  
Dong-Yun Zhan ◽  
Cheng-Kun Du ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dilated Cardiomyopathy ◽  
Glycogen Synthase ◽  
Troponin T ◽  
Systolic Function ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Myosin Heavy Chain Isoform ◽  
Familial Dilated Cardiomyopathy ◽  
Gsk 3Β

Glycogen synthase kinase-3β (GSK-3β) plays a central role in both cardiac physiology and pathology. Herein we want to clarify the role of GSK-3β in familial dilated cardiomyopathy. We generated a mouse model carrying a heterozygous knockout mutation of GSK-3β (GSK-3β+/− KO), together with a ΔK210 knockin mutation in cardiac troponin T (ΔK210 cTnT KI), which was proved to be one of the genetic causes of familial dilated cardiomyopathy (DCM). GSK-3β+/− KO prevented the slow and rapid deterioration in left ventricular systolic function accompanying heart failure (HF) in DCM mice with heterozygous and homozygous ΔK210 cTnT KI mutations, respectively. GSK-3β+/− KO also prevented cardiac enlargement, myocardial fibrosis, and cardiomyocyte apoptosis and markedly reduced the expression of cardiac β-myosin heavy chain isoform, indicative of HF, in DCM mice with homozygous ΔK210 cTnT KI mutation. GSK-3β+/− KO also extended the life span of these DCM mice. This study suggests that the inhibition of GSK-3β is cardioprotective in familial DCM associated with ΔK210 cTnT mutation.

scholarly journals Cardiomyocyte‐GSK‐3β deficiency induces cardiac progenitor cell proliferation in the ischemic heart through paracrine mechanisms

2021 ◽  
Author(s):  
Ayesha M. Yusuf ◽  
Rizwan Qaisar ◽  
Abaher O. Al‐Tamimi ◽  
Manju Nidagodu Jayakumar ◽  
James R. Woodgett ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cell ◽  
Ischemic Heart ◽  
Cardiac Progenitor Cell ◽  
Progenitor Cell Proliferation ◽  
Gsk 3Β

scholarly journals Impact of Maturation on Myocardial Response to Ischemia and the Effectiveness of Remote Preconditioning in Male Rats

2021 ◽  
Vol 22 (20) ◽  
pp. 11009
Author(s):  
Lucia Kindernay ◽  
Veronika Farkasova ◽  
Jan Neckar ◽  
Jaroslav Hrdlicka ◽  
Kirsti Ytrehus ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ventricular Arrhythmias ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Age Groups ◽  
Left Ventricular ◽  
Male Rats ◽  
Mature Adult ◽  
Survival Proteins

Aging attenuates cardiac tolerance to ischemia/reperfusion (I/R) associated with defects in protective cell signaling, however, the onset of this phenotype has not been completely investigated. This study aimed to compare changes in response to I/R and the effects of remote ischemic preconditioning (RIPC) in the hearts of younger adult (3 months) and mature adult (6 months) male Wistar rats, with changes in selected proteins of protective signaling. Langendorff-perfused hearts were exposed to 30 min I/120 min R without or with prior three cycles of RIPC (pressure cuff inflation/deflation on the hind limb). Infarct size (IS), incidence of ventricular arrhythmias and recovery of contractile function (LVDP) served as the end points. In both age groups, left ventricular tissue samples were collected prior to ischemia (baseline) and after I/R, in non-RIPC controls and in RIPC groups to detect selected pro-survival proteins (Western blot). Maturation did not affect post-ischemic recovery of heart function (Left Ventricular Developed Pressure, LVDP), however, it increased IS and arrhythmogenesis accompanied by decreased levels and activity of several pro-survival proteins and by higher levels of pro-apoptotic proteins in the hearts of elder animals. RIPC reduced the occurrence of reperfusion-induced ventricular arrhythmias, IS and contractile dysfunction in younger animals, and this was preserved in the mature adults. RIPC did not increase phosphorylated protein kinase B (p-Akt)/total Akt ratio, endothelial nitric oxide synthase (eNOS) and protein kinase Cε (PKCε) prior to ischemia but only after I/R, while phosphorylated glycogen synthase kinase-3β (GSK3β) was increased (inactivated) before and after ischemia in both age groups coupled with decreased levels of pro-apoptotic markers. We assume that resistance of rat heart to I/R injury starts to already decline during maturation, and that RIPC may represent a clinically relevant cardioprotective intervention in the elder population.

Role of GSK-3 in Cardiac Health: Focusing on Cardiac Remodeling and Heart Failure

2021 ◽  
Vol 22 ◽  
Author(s):  
Ubaid Tariq ◽  
Shravan Kumar Uppulapu ◽  
Sanjay K Banerjee
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Cardiac Development ◽  
Glycogen Synthase ◽  
Cardiac Regeneration ◽  
Negative Regulator ◽  
Cell Cycle Regulators ◽  
Cardiomyocyte Proliferation ◽  
Gsk 3Β

: Glycogen synthase kinase 3 (GSK-3) is a ubiquitously expressed serine/threonine kinase and was first identified as a regulator of glycogen synthase enzyme and glucose homeostasis. It regulates cellular processes like cell proliferation, metabolism, apoptosis and development. Recent findings suggest that GSK-3 is required to maintain the normal cardiac homeostasis that regulates cardiac development, proliferation, hypertrophy and fibrosis. GSK-3 is expressed as two isoforms, α and β. Role of GSK-3α and GSK-3β in cardiac biology is well documented. Both isoforms have common as well as isoform-specific functions. Human data also suggests that GSK-3β is downregulated in hypertrophy and heart failure, and acts as a negative regulator. Pharmacological inhibition of GSK-3α and GSK-3β leads to the endogenous cardiomyocyte proliferation and cardiac regeneration by inducing the upregulation of cell cycle regulators, which results in cell cycle re-entry and DNA synthesis. It was found that cardiac specific knockout (KO) of GSK-3α retained cardiac function, inhibited cardiovascular remodelling and restricted scar expansion during ischemia. Further, knockout of GSK-3α decreases cardiomyocyte apoptosis and enhances its proliferation. However, GSK-3β KO also results in hypertrophic myopathy due to cardiomyocyte hyper-proliferation. Thus GSK-3 inhibitors are named as a double-edged sword because of their beneficial and off target effects. This review focuses on the isoform specific functions of GSK-3 that will help in better understanding about the role of GSK-3α and GSK-3β in cardiac biology and pave a way for the development of new isoform specific GSK-3 modulator for the treatment of ischemic heart disease, cardiac regeneration and heart failure.

PANC-1 cells proliferative response to ionizing radiation is related to GSK-3β phosphorylation

2012 ◽  
Vol 90 (6) ◽  
pp. 779-790 ◽  
Author(s):  
Nora A. Mohamad ◽  
Graciela P. Cricco ◽  
Claudia M. Cocca ◽  
Elena S. Rivera ◽  
Rosa M. Bergoc ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Ionizing Radiation ◽  
Catalase Activity ◽  
Glycogen Synthase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Γ Irradiation ◽  
Irreversible Inhibitor ◽  
Gsk 3Β

Radiotherapy may be used to treat pancreatic cancer and relieve pain. We have previously reported that histamine modulates pancreatic adenocarcinoma PANC-1 cell proliferation. This work was aimed to evaluate whether histamine improves radiosensitivity of PANC-1 cells in relation to phosphorylation/inhibition of glycogen synthase kinase-3β (GSK-3β). Immediately after γ irradiation, intracellular hydrogen peroxide was markedly decreased together with a rapid increase in catalase activity. Although histamine diminished catalase activity in nonirradiated cells, it only partially hindered the increase observed in irradiated cells and could not modify radiosensitivity. In control cells, a high expression of total and a very low expression of phosphorylated/inactive GSK-3β were found. An increment in reactive oxygen species levels produced an augmentation in GSK-3β phosphorylation and suppressed cell proliferation. In both control and histamine-treated irradiated cells, the rise in catalase activity lowered reactive oxygen species levels and only a small increase in phosphorylated GSK-3β was detected. Alternatively, 3-aminotriazole, an irreversible inhibitor of catalase, reduced the survival fraction in irradiated control cells along with an increment in phosphorylated GSK-3β. These results suggest that upon irradiation, early catalase activation may be responsible for keeping GSK-3β active conceding cells a survival advantage toward cytotoxic effects of ionizing radiation.

Abstract 16161: GSK-3β Activates Autophagy and Protects Against Cardiac Aging Through Ulk1

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Peiyong Zhai ◽  
Akihiro Shirakabe ◽  
Takanobu Yamamoto ◽  
Yoshiyuki Ikeda ◽  
Bonaventure Magrys ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Glycogen Synthase ◽  
Left Ventricular ◽  
Protective Mechanism ◽  
Cross Sectional ◽  
Cardiac Aging ◽  
Beneficial Effects ◽  
Stiffness Constant ◽  
Age Related ◽  
Gsk 3Β

Accumulating lines of evidence suggest that glycogen synthase kinase-3β (GSK-3β) is involved in aging. However, the effects of GSK-3β on cardiac aging and the underlying mechanisms remain to be elucidated. Autophagy, a protective mechanism in aging, decreases with age. We hypothesized that GSK-3β attenuates cardiac aging via Ulk1, a regulator of autophagy, and studied constitutively active GSK-3βS9A knock-in mice (βKI), GSK-3βS9A/Ulk1+/- bigenic mice (Bigenic), and GSK-3β+/- mice (βKO) up to 24 months (M) of age. Left ventricular (LV) weight/body weight (LVW/BW, mg/g) was not significantly different among wild-type mice (WT), βKI and βKO at 6M. It was lower in βKI (2.4±0.1, p<0.005) and higher in βKO (4.8±0.8, p<0.05) than in WT (3.8±0.2) at 24M. Cardiomyocyte cross-sectional area (CSA, μm2) was smaller in βKI (360±9, p<0.001) but bigger in βKO (540±11, p<0.01) than in WT (502±5) at 24M. The LVW/BW was greater (3.5±0.2, p<0.001) and the CSA was bigger (527±4, p<0.001) in Bigenic than in βKI at 24M. These data demonstrate that GSK-3β inhibits age-dependent cardiac hypertrophy via Ulk1. Cardiac fibrosis (%) was more in βKO (5.4±0.1, p<0.001) and less in βKI (2.4±0.1, p<0.001) than in WT (4.0±0.3) at 24M. There was much more fibrosis in Bigenic (5.5±0.6, p<0.001) than in βKI at 24M. These data show that GSK-3β reduces age-related cardiac fibrosis via Ulk1. LV end-systolic elastance (Ees, mmHg/μl) and chamber stiffness constant (CSC, μl-1) were not significantly different among WT, βKI, and βKO at 6M. At 24M, the Ees was lower in βKO (4±1, p<0.05) and higher in βKI (12±3, p<0.05) than in WT (7±0), and the CSC was higher in βKO (0.19±0.01, p<0.001) and lower in βKI (0.06±0.01, p<0.001) than in WT (0.14±0.01). The beneficial effects of GSK-3β on cardiac function were abolished in the Bigenic, indicating that GSK-3β prevents age-specific cardiac dysfunction via Ulk1. The level of p62, a protein degraded by autophagy, was lower in βKI and higher in βKO than in WT. The numbers of autophagosomes and autolysosomes were significantly greater in βKI/tfLC3 (tandem fluorescent mRFP-GFP-LC3) mice than in tfLC3 or βKI/tfLC3/Ulk1+/- mice. These data suggest that GSK-3β activates autophagy via Ulk1. In conclusion, GSK-3β attenuates cardiac aging by activating Ulk1-dependent autophagy.

Abstract 69: Cardiomyocyte GSK-3α Signaling Exacerbate Pressure Overload-induced Dilated Cardiomyopathy and Heart Failure

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Firdos Ahmad ◽  
Hind Lal ◽  
Vipin K Verma ◽  
Qinkun Zhang ◽  
James R Woodgett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Tamoxifen Treatment ◽  
Control Group ◽  
Lv Remodeling

Chronic pressure-overload (PO) induced-dilated cardiomyopathy (DCM) is one of the leading causes of left ventricular (LV) remodeling and heart failure. The role of glycogen synthase kinase-3α (GSK-3α) in PO-induced remodeling is not clear and existing dataset with global transgenic and knockout (KO) models show opposing roles. We sought to identify the specific role of GSK-3α in PO-induced dilatative cardiac remodeling. To better understand the role of GSK-3α, we employed cardiomyocyte-specific GSK3A ( GSK3A fl/fl MerCreMer ) KO mice. Post-tamoxifen treatment, the GSK-3α KO and littermate control mice underwent sham or trans-aortic constriction (TAC) surgery. Heart function was assessed at 0, 2, 4 and 6 week post-TAC using serial M-mode echocardiography. Cardiac function in the KOs and littermate controls declines equally up to 2 weeks of TAC. At 4 week, KO hearts underwent further hypertrophy, retaining concentric LV remodeling and preserved contractile function both at systole and diastole. In contrast, wild-type LV showed significant chamber dilatation with an impaired contractility. Significantly reduced LV chamber dilatation [LVIDd(mm); 5.4±0.4 vs. 4.9±0.4, P =0.01] and preserved contractile function [LVEF(%); 22.2±12.6 vs. 40.0±18.7, P =0.02] remains same in the KO mice until the end of the study (6 wk). Furthermore, LV posterior wall thickness in the KO hearts, both at systole and diastole, were significantly greater in comparison to the controls. Consistent with preserved LV dimension, significantly less mortality was observed in the KO vs. control group during the remodeling phase. Histological analysis of heart sections further revealed better preserved LV chamber and protection against TAC-induced cellular hypertrophy in the GSK-3α KOs. Moreover, KO hearts showed significantly less fibrosis accompanied with low level of cardiomyocyte apoptosis post-6 wk of TAC. Taken together, these observations show that cardiomyocyte-specific deletion of GSK-3α protects against chronic PO-induced adverse LV remodeling and preserves contractile function. Inhibiting specifically GSK-3α using isoform-specific inhibitor could be a viable therapeutic strategy to limit the PO-induced DCM, adverse remodeling and heart failure.

Abstract 12999: Senescence Marker Protein 30 Protect the Cardiac Injury From After Ischemia Reperfusion

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shinpei Kadowaki ◽  
Tetsuro Shishido ◽  
Taro Narumi ◽  
Yuki Honda ◽  
Satoshi Nishiyama ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Marker Protein ◽  
Age Related ◽  
Ribosomal S6 Kinase ◽  
Gsk 3Β

Background: Successful myocardial reperfusion is effective therapy for improving the clinical outcome after acute myocardial infarction, nevertheless reperfusion injury can paradoxically induces cardiomyocyte dysfunction. Moreover, recovery of cardiac function is impaired with aging. Glycogen synthase kinase-3β (GSK-3β) and p70 ribosomal S6 kinase (p70S6K) are cardioprotective against I/R via mitochondrial dysfunction. Senescence marker protein-30 (SMP30), which regulates mitochondrial quality and decreases with aging, is an organ-protective protein; however the protective role of SMP30 against ischemia/reperfusion (I/R) has not been clearly determined yet. Methods and Result: Firstly, we confirmed that SMP30 expressions in the heart were progressively decreased with aging. In vitro study, we also found that reactive oxygen species decreased expression levels of SMP30 in neonatal cardiomyocyte. Depletion of SMP30 increased apoptotic cardiomyocyte death after hydrogen peroxide stimulation. To evaluate the cardioprotective role of SMP30, we induced 30 min ischemia and 24-hr reperfusion (I/R) in WT and SMP30 KO mice. Phosphorylation levels of p70S6K and GSK-3β in the heart were increased after IR in WT mice; however those phosphorylation were attenuated in SMP30 KO mice. SMP30 KO mice after I/R had significantly larger numbers of apoptotic cardiomyocyte than WT mice ( 10.5± 5.7% vs. 4.0± 1.7%, p < 0.05), that correlated with a significant expansion in infarct size and a significant reduction of left ventricular fractional shortening (37.3± 4.3% vs 43.4± 5.1%, p < 0.01). Conclusions: These results suggest that reduction of SMP30 levels with aging is associated with age-related dysfunction after ischemia-reperfusion through disability to phosphorylate p70S6K and GSK-3β. Thus, SMP30 might be a novel therapeutic target for the treatment of acute myocardial infarction in elderly patient.

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