• Korean Circulation Journal
• /
• 제53권3호
• /
• pp.151-167
• /
• 2023

Background and Objectives: Acute myocardial infarction (AMI) often occurs suddenly and leads to fatal consequences. Ferroptosis is closely related to the progression of AMI. However, the specific mechanism of ferroptosis in AMI remains unclear. Methods: We constructed a cell model of AMI using AC16 cells under oxygen and glucose deprivation (OGD) conditions and a mice model of AMI using the left anterior descending (LAD) ligation. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide was employed to determine cell viability. The levels of lactate dehydrogenase, creatine kinase, reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and iron were measured using corresponding kits. Dual luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull-down were performed to validate the correlations among AC005332.7, miR-331-3p, and cyclin D2 (CCND2). Hematoxylin and eosin staining was employed to evaluate myocardial damage. Results: AC005332.7 and CCND2 were lowly expressed, while miR-331-3p was highly expressed in vivo and in vitro models of AMI. AC005332.7 sufficiency reduced ROS, MDA, iron, and ACSL4 while boosting the GSH and GPX4, indicating that AC005332.7 sufficiency impeded ferroptosis to improve cardiomyocyte injury in AMI. Mechanistically, AC005332.7 interacted with miR-331-3p, and miR-331-3p targeted CCND2. Additionally, miR-331-3p overexpression or CCND2 depletion abolished the suppressive impact of AC005332.7 on ferroptosis in OGD-induced AC16 cells. Moreover, AC005332.7 overexpression suppressed ferroptosis in mice models of AMI. Conclusions: AC005332.7 suppressed ferroptosis in OGD-induced AC16 cells and LAD ligation-operated mice through modulating miR-331-3p/CCND2 axis, thereby mitigating the cardiomyocyte injury in AMI, which proposed novel targets for AMI treatment.

• 대한핵의학회지
• /
• 제27권2호
• /
• pp.191-194
• /
• 1993

탈륨 부하영상을 얻은 후 4시간 휴식기재분포영상을 얻는 대신 휴식상태에서 탈륨 재주사를 하고 재주사영상만을 얻는 방법을 시도하는 경우 어느 정도에서 오진을 할 것인가를 알아보기 위해 본 연구를 전향적으로 시행하였다. 디피리다몰부하 탈륨신티그라피를 시행하면서 부하-재분포-재주사 영상을 모두 얻을 수 있었던 63예의 환자를 대상으로 하였으며, 모두에서 디피리다몰(0.56 mg/Kg) 부하법을 사용하였다. 영상기기는 Sopha DSX SPECT를 사용하였으며, 좌심실은 5개 부위로 나누어 석하였고, 섭취정도는 정상(3), 약간 감소(2), 감소(1), 섭취없음(0)으로 4등분하였으며, 한 등급 이상의 변화가 있으면 변화가 있는 것으로 평가하였다. 탈륨부하영상에서 이상소견을 보인 100개 부위 중 재분포영상에서 한등급 이상의 재분포를 보인 부위는 52개였으며, 재주사영상에서 오히려 섭취가 감소되는 것처럼 보인 부위는 17개(32.7%)였다. 이 중 11개부위(21.2%)는 섭취감소의 정도가 심하여 휴식기재분포 영상을 참조하지 않고 부하영상과 재주사영상만으로 판독한다면 심근경색으로 오진할 수밖에 없었다. 휴식기재분포 영상에서 고정관류결손을 보인 32개 부위 중 15개부위 (46.9%)는 재주사 영상에서 섭취가 증가되었다. 결론적으로 탈륨재주사영상법이 생존심근을 진단하는데 매우 유용한 방법임에는 틀림이 없으나, 부하영상을 얻은 후 휴식기재분포영상을 얻지 않고 바로 재주사영상만을 얻는다면 상당한 수에서는 오히려 허혈심근을 심근경색으로 오진할 수 있으므로, 탈륨 심근시티그라피의 경우 부하영상-휴식기재분포영상을 촬영한 후 고정관류 결손을 보이는 환자에서만 재주사영상을 얻는 것이 타당하다고 사료되었다.

• Molecules and Cells
• /
• 제19권3호
• /
• pp.402-407
• /
• 2005

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as ${\alpha}$-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of $5.0{\times}10^5$ FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated $Ca^{2+}$ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.

• IMMUNE NETWORK
• /
• 제22권6호
• /
• pp.49.1-49.15
• /
• 2022

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H₂O₂-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H₂O₂-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.

• Journal of Microbiology and Biotechnology
• /
• 제31권8호
• /
• pp.1069-1078
• /
• 2021

Sevoflurane postconditioning (SPostC) has been proved effective in cardioprotection against myocardial ischemia/reperfusion injury. It was also reported that heat shock protein 70 (HSP70) could be induced by sevoflurane, which played a crucial role in hypoxic/reoxygenation (HR) injury of cardiomyocytes. However, the mechanism by which sevoflurane protects cardiomyocytes via HSP70 is still not understood. Here, we aimed to investigate the related mechanisms of SPostC inducing HSP70 expression to reduce the HR injury of cardiomyocytes. After the HR cardiomyocytes model was established, the cells transfected with siRNA for HSP70 (siHSP70) or not were treated with sevoflurane during reoxygenation. The lactate dehydrogenase (LDH) level was detected by colorimetry while cell viability and apoptosis were detected by MTT and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect HSP70, apoptosis-, cell cycle-associated factors, iNOS, and Cox-2 expressions. Enzyme-linked immuno sorbent assay (ELISA) was used to measure malondialdehyde (MDA) and superoxide dismutase (SOD). SPostC decreased apoptosis, cell injury, oxidative stress and inflammation and increased viability of HR-induced cardiomyocytes. In addition, SPostC downregulated Bax and cleaved caspase-3 levels, while SPostC upregulated Bcl-2, CDK-4, Cyclin D1, and HSP70 levels. SiHSP70 had the opposite effect that SPostC had on HR-induced cardiomyocytes. Moreover, siHSP70 further reversed the effect of SPostC on apoptosis, cell injury, oxidative stress, inflammation, viability and the expressions of HSP70, apoptosis-, and cell cycle-associated factors in HR-induced cardiomyocytes. In conclusion, this study demonstrates that SPostC can reduce the HR injury of cardiomyocytes by inducing HSP70 expression.

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권5호
• /
• pp.325-333
• /
• 2022

Heart failure (HF) has become one of the severe public health problems. The detailed role of mitochondrial function in HF was still unclear. Benzoylaconine (BAC) is a traditional Chinese medicine, but its role in HF still needs to be explored. In this study, oxygen-glucose deprivation and reperfusion (OGD/R) was executed to mimic the injury of H9C2 cells in HF. The viability of H9C2 cells was assessed via MTT assay. OGD/R treatment markedly decreased the viability of H9C2 cells, but BAC treatment evidently increased the viability of OGD/R-treated H9C2 cells. The apoptosis of H9C2 was enhanced by OGD/R treatment but suppressed by BAC treatment. The mitochondrial membrane potential was evaluated via JC-1 assay. BAC improved the mitochondrial function and suppressed oxidative stress in OGD/R-treated H9C2 cells. Moreover, Western blot analysis revealed that the protein expression of p-AMPK and PGC-1α were reduced in OGD/R-treated H9C2 cells, which was reversed by BAC. Rescue assays indicated that AMPK attenuation reversed the BAC-mediated protective effect on OGD/R-treated cardiomyocytes. Moreover, BAC alleviated myocardial injury in vivo. In a word, BAC modulated the mitochondrial function in OGD/R-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis. The findings might provide support for the application of BAC in the treatment of HF.

• 대한핵의학회지
• /
• 제26권2호
• /
• pp.274-279
• /
• 1992

Clinical role of $^{99m}Tc-MIBI$ myocardial scintigraphy in the diagnosis of coronary artery disease (CAD) is now well accepted, however, the role of it in the identification of viable myocardium in patients with chronic CAD has not yet been clarified. To determine the usefulness of rest-injected $^{99m}Tc-MIBI$ scan as a marker of myocardial viability, the regional uptake of this agent at rest was compared with that of $^{201}Tl$ on reinjection and 24 hours after reinjection images. Subject patients were 13 chronic CAD patients who showed irreversible perfusion defect(s) on standard pharmacologic (dipyridamole) stress-redistribution images. Immediately after the redistribution images were obtained, 37 MBq thallium was injected at rest, and images were reacquired at 10 minutes and 24 hours after reinjection. After then 740 MBq $^{99m}Tc-MIBI$ was injected, and 1 hour later rest MIBI myocardial imaging was performed. Five sets of imagestress, redistribution, reinjection, delayed images of thallium, and rest image of MIBI) were then analyzed qualitatively and quantitatively. Left ventricle was arbitrarily divided into 9 segments (apex, basal and apical portions of anterior, septal, inferior, and lateral walls). Seven patients and 30 regions showed a fixed perfusion defect on the stress-redistribution images. Among 30 regions, 15 showed positive uptakes and 6 showed negative uptakes on both $^{201}Tl$ reinjection/delayed images and $^{99m}Tc-MIBI$ rest images. Five regions showed only thallium uptake and were regarded as viable clinically. Of four regions which showed only $^{99m}Tc-MIBI$ uptake, two were regarded as viable, while the other two were regarded as a nonviable scar tissue clinically. In conclusion, $^{201}Tl$ reinjection technique was more reliable in the identification of viable myocardium. However, the role of $^{99m}Tc-MIBI$ in identification of viable myocardium was still remained to be clarified because 2 of 9 regions showed only $^{99m}Tc-MIBI$ uptake and were regarded as viable tissues.

• Journal of Ginseng Research
• /
• 제47권6호
• /
• pp.755-765
• /
• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• 대한핵의학회지
• /
• 제39권4호
• /
• pp.224-230
• /
• 2005

목적: 심근의 최대탄성도는 전부하 후부하에 독립적인 지표로서 SPECT를 이용하여 좌심실의 국소탄성도($rE_{max}$)를 비침습적으로 측정하였다. 게이트 심근 SPECT 영상에서 국소부피변화를 얻고, 요골동맥 긴장도를 측정하여 중심동맥의 압력 곡선을 얻어 측정한 최대탄성도를 관상동맥우회로 수술 전후 환자를 대상으로 수술전후 관류 및 기능지표와 비교하여보았다. 대상 및 방법: 관상동맥우회로 수술이 결정되어 시행한 환자 21명(남:여=17:4, $58{\pm}12$세)을 대상으로 $^{201}TI$ 휴식기 영상과 디피리다몰 부하 $^{99m}Tc$-sestamibi 게이트 SPECT를 수술전과 수술 후 3개월째 시행하였다. 동시에 요골동맥으로부터 압력곡선을 얻었다. 기능과의 관계를 보기 위해서 관류와 심벽두꺼워짐을 탄성도와 비교하였으며, 심벽두꺼워짐이 20%미만일 때 수술 후 10%이상 호전되지 않는 기능이상 분절에 대해 수술 전후의 탄성도를 비교하였다. 결과: 수술 전 탄성도가 $2.41{\pm}1.64$ mmHg/mL에서 $2.78{\pm}1.83$ mmHg/mL 으로 수술 후에 증가하였으나, 관류와 심벽두꺼워짐과는 낮은 상관성을 보였다. (r=0.35, p<0.001). 관류 60% 이상의 분절에서는 $2.65{\pm}1.67$ mmHg/mL 이었으나, 관류나 낮은 분절의 탄성도는 $1.30{\pm}1.24$ mmHg/mL 였다. 심벽두꺼워짐이 40% 이상 되는 분절의 수술 전 탄성도는 $3.01{\pm}1.92$ mmHg/mL 였고, 기능이 조금 약한 부분인 40%에서 20% 사이의 심벽두꺼워짐 값을 가진 분절에서는 $2.40{\pm}1.19$ mmHg/mL로 심각한 기능이상을 반영하는 20%미만 분절의 탄성도는 $1.13{\pm}0.89$ mmHg/mL의 분포를 보였다. 수술 전 심벽두꺼워짐이 20% 미만일 때 수술 후 10%이상 회복을 보인 생존심근와 그렇지 않은 비생존심근사이의 수술 전후 탄성도는 $1.27{\pm}1.07$ mmHg/mL에서 $1.79{\pm}1.48$ mmHg/mL, $0.97{\pm}0.59$ mmHg/mL에서 $1.22{\pm}0.71$ mmHg/mL로 생존심근의 수술 후 값의 향상이 조금 더 높았다. 그러나, 심벽두꺼워짐의 정도가 탄성도 높아짐의 정도 사이에는 상관성이 없었다(r=0.007). 결론: 수술 전 $rE_{max}$는 관류와 심벽두꺼워짐과 상관성이 약하게 있었다. 기능이상이면서 생존능이 있는 심근의 탄성도는 수술 후 증가하였지만 심벽두꺼워짐의 향상과는 상관성이 없었다. 심근기능의 전부하 후부하에 독립적인 지표인 탄성도는 실제 부피의 증가와 연관되지 않으면서도 생존능이 있는 심근의 기준과 일치하는 양상을 보였으므로 독립적인 매개변수로 사용될 수 있을 것으로 기대한다.

• 대한핵의학회지
• /
• 제25권2호
• /
• pp.177-185
• /
• 1991

Dipyridamole thallium imaging is one of the most widely accepted means of evaluating patients with suspected or known coronay artery disease. The results of thallium imaging help diagnose coronary artery disesse (CAD), determine the hemodynamic significance of coronary stenosis, evaluate viability of myocardium, assess the outcome of therapeutic interventions and stratify patients according to their risk for luther cardiac events. An increased lung thallium uptake and transient LV dilation has been reported as poor prognostic indicator and associated with extensive and severe coronary artery disease. We quantitated lung/heart uptake ratio (l/HUR) and transient left ventricular dilation ratio in 44 patients and 17 controls undertaking dipyridamole thallium-201 scintigraphy. The results are as follows: 1) The lung/heart uptake ratio was high in patients with CAD and which became higher according to increasing number of diseased vessel. The L/HUR of patients with low LVEF (<35%) was lower than those with normal LVEF. 2) Transient left ventricular dilation ratio of CAD patients had no close relation between numbers of diseased vessels and was not higher than normals. But transient left ventricular dilation ratio of patients with myocardial infartion was higher than normals. We concluded that lung/heart uptake ratio seems to be sensitive marker for severity of CAD and myocardial function, but transient left ventricular dilation ratio alone is not sufficient to be a marker for severe and extensive CAD.