scholarly journals Extracorporeal Shock Wave-Supported Adipose-Derived Fresh Stromal Vascular Fraction Preserved Left Ventricular (LV) Function and Inhibited LV Remodeling in Acute Myocardial Infarction in Rat

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Tsung-Cheng Yin ◽  
Christopher Glenn Wallace ◽  
Kuan-Hung Chen ◽  
Pei-Lin Shao ◽  
...  

This study tested the hypothesis that extracorporeal shock wave- (ECSW-) assisted adipose-derived stromal vascular fraction (SVF) therapy could preserve left ventricular ejection fraction (LVEF) and inhibit LV remodeling in a rat after acute myocardial infarction (AMI). Adult male SD rats were categorized into group 1 (sham control), group 2 (AMI induced by left coronary artery ligation), group 3 [AMI + ECSW (280 impulses at 0.1 mJ/mm2, applied to the chest wall at 3 h, days 3 and 7 after AMI), group 4 [AMI + SVF (1.2 × 106) implanted into the infarct area at 3 h after AMI], and group 5 (AMI + ECSW-SVF). In vitro, SVF protected H9C2 cells against menadione-induced mitochondrial damage and increased fluorescent intensity of mitochondria in nuclei (p<0.01). By day 42 after AMI, LVEF was highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, and similar between the latter two groups (all p<0.0001). LV remodeling and infarcted, fibrotic, and collagen deposition areas as well as apoptotic nuclei exhibited an opposite pattern to LVEF among the groups (all p<0.0001). Protein expressions of CD31/vWF/eNOS/PGC-1α/α-MHC/mitochondrial cytochrome C exhibited an identical pattern, whilst protein expressions of MMP-9/TNF-α/IL-1β/NF-κB/caspase-3/PARP/Samd3/TGF-β/NOX-1/NOX-2/oxidized protein/β-MHC/BNP exhibited an opposite pattern to LVEF among five groups (all p<0.0001). Cellular expressions of CXCR4/SDF-1α/Sca-1/c-Kit significantly and progressively increased from groups 1 to 5 (all p<0.0001). Cellular expression of γ-H2AX/CD68 displayed an opposite pattern to LVEF among the five groups (all p<0.0001). In conclusion, ECSW-SVF therapy effectively preserved LVEF and inhibited LV remodeling in rat AMI.

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 167
Author(s):  
Jiunn-Jye Sheu ◽  
Han-Tan Chai ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
Yi-Ling Chen ◽  
...  

This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.


2021 ◽  
Author(s):  
Yen‐Ta Chen ◽  
Fei-Chi Chuang ◽  
Chih‐Chao Yang ◽  
John Y. Chiang ◽  
Pei‐Hsun Sung ◽  
...  

Abstract Background: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cell (ADMSC) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and Results: Male-adult SD rats (n=30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720 degrees counterclockwisely for 2h, then detorsion (i.e., reperfusion) to the original position for 72h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 minutes after ischemia, followed by 20 mg at 3h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSC/1.2 x 106 cells/intravenous administration at 30 minutes after ischemia, followed by days 1/2 TTIR) and group 5 (TTIR + Mel + ADMSC). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C) and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2 and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p<0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p<0.0001).Conclusion: Mel-ADMSCs effectively protected the testis against TTIR injury.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Arivazhagan Palaniyappan ◽  
Halliday Idikio ◽  
Bodh I Jugdutt

Recent evidence suggests that aging alters the expression of inflammatory cytokines, impairs healing and promotes adverse left ventricular (LV) remodeling after chronic reperfused ST-segment elevation myocardial infarction (RSTEMI). Whether aging alters the expression of angiotensin II type 1 (AT 1 ) and type 2 (AT 2 ) receptors, and angiotensin-converting-enzyme-2 (ACE-2), angiotensin (Ang) (1–7), N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) and Smad-2 proteins early after acute RSTEMI is not known. AT 2 receptors have been implicated in cardioprotection, ACE-2 and Ang (1–7) in the counter-regulatory arm of the renin-angiotensin-system (RAS) and Ac-SDKP in inflammation and collagen synthesis. We hypothesized that aging is associated with downregulation of AT 2 receptors and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins. We compared in-vivo LV remodeling and function (echocardiography/Doppler) and the ex-vivo molecular expression of AT 1 and AT 2 receptors, ACE-2, Ang (1–7) and Ac-SDKP after acute RSTEMI (90 min no-flow ischemia and 120 min reperfusion) in young (group 1, n=12) and old (group 2, n=12) dogs. Compared to group 1 controls, group 2 hearts showed more severe echocardiographic LV remodeling and dysfunction (with lower ejection fraction, larger volumes and more diastolic dysfunction, infarct expansion and thinning). In addition, group 2 hearts showed no change in AT 1 receptor protein and decrease in AT 2 receptor protein and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins in the reperfused ischemic zone. The findings suggest that aging is associated with changes in proteins in the regulatory as well as the counter-regulatory arm of the RAS during acute RSTEMI. The age-related downregulation of AT 2 receptors, ACE-2, Ang (1–7), Ac-SDKP and Smad-2 may contribute to the more severe LV remodeling and dysfunction after acute RSTEMI. Targeting these proteins early during reperfusion may improve outcome in acute RSTEMI.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yen-Ta Chen ◽  
Fei-Chi Chuang ◽  
Chih-Chao Yang ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
...  

Abstract Background This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and results Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). Conclusion Mel-ADMSCs effectively protected the testis against TTIR injury.


2021 ◽  
Vol 30 ◽  
pp. 096368972110070
Author(s):  
Jui-Ning Yeh ◽  
Ruan-Ruan Yang ◽  
Christopher Glenn Wallace ◽  
Chi-Ruei Huang ◽  
Yi-Ching Chu ◽  
...  

This study tested the impact of single dose and two doses of endothelial progenitor cells (EPCs) and EPCs-derived condition medium (CM) on protecting the left-ventricular myocardium (LVM) from acute ischemia-reperfusion (IR) injury. In vitro study showed EPCs and CM had comparably higher capacity for enhancement of angiogenesis as compared with the controls (all P < .001). Adult-male SD rats ( n = 36) were equally categorized into groups 1 (sham-operated control), 2 (IR+vehicle), 3 [IR+EPCs/1.2 × 106/intravenous administration at 3 h after IR procedure), 4 (IR+EPCs/1.2 × 106/at 3 h/24 h after IR), 5 (IR+CM/3.0cc/intravenous administration at 3 h after IR), 6 (IR+EPCs/3.0cc/at 3h/24 h after IR), and euthanized by day 3 after IR. The left-ventricular-ejection-fraction, protein and cellular expressions of endothelial-cell markers (CD31/vWF), small vessel number and protein expression of mitochondrial (mitochondrial-cytochrome-C) integrity were highest in group 1, lowest in group 2, significantly higher in group 4 than in groups 3/5/6 and significantly higher in groups 3/6 than in group 5 but they showed no differences in groups3/6, whereas the protein expressions of apoptotic (cleaved-caspase 3/cleaved-PARP), fibrotic (Smad3/TGF-ß), mitochondrial-damaged (cytosolic-cytochrome-C), heart-failed/pressure-overload (BNP), oxidative-stress (p47phox/NOX-1/NOX-2/oxidized protein), and autophagic (LCB3-II/LCB3-I) biomarkers and fibrotic/collagen-deposition areas exhibited an opposite pattern to endothelial-cell markers (all P < .0001). The protein expressions of angiogenesis (VEGF/SDF-1α/CXCR4/HIF-1α) were lowest in group 1, highest in group 4, significantly higher in groups 3/6 than in groups 2/5, significantly higher in group 5 than in group 2, but they showed no difference between groups 3/6 (all P < .0001). These results demonstrate that two consecutive doses of EPC/CM were superior to just one at protecting LVM against IR injury.


Author(s):  
Malgorzata Zalewska-Adamiec ◽  
Jolanta Malyszko ◽  
Ewelina Grodzka ◽  
Lukasz Kuzma ◽  
Slawomir Dobrzycki ◽  
...  

Abstract Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes about 10% of the cases of acute coronary syndromes (ACS). It is a working diagnosis and requires further diagnostics to determine the cause of ACS. Methods In this study, 178 patients were initially diagnosed with MINOCA over a period of 3 years at the Department of Invasive Cardiology of the University Clinical Hospital in Białystok. The value of estimated glomerular filtration rate (eGFR) was calculated for all patients. The patients were divided into 2 groups depending on the value of eGFR: group 1—53 patients with impaired kidney function (eGFR < 60 mL/min/1.73 m2; 29.8%) and group 2—125 patients with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2; 70.2%). Results In group 1, the mean age of patients was significantly higher than that of group 2 patients (77.40 vs 59.27; p < 0.0001). Group had more women than group 2 (73.58% vs 49.60%; p = 0.003). Group 1 patients had higher incidence rate of arterial hypertension (92.45% vs 60.80%; p < 0.0001) and diabetes (32.08% vs 9.60%; p = 0.0002) and smoked cigarettes (22.64% vs 40.80%; p = 0.020). Group 1 patients had higher incidence rate of pulmonary edema, cardiogenic shock, sudden cardiac arrest (13.21% vs 4.00%; p = 0.025), and pneumonia (22.64% vs 6.40%; p = 0.001). After the 37-month observation, the mortality rate of the patients with MINOCA was 16.85%. Among group two patients, more of them became deceased during hospitalization (7.55% vs 0.80%; p = 0.012), followed by after 1 year (26.42% vs 7.20%; p = 0.0004) and after 3 years (33.96% vs 9.6%; p < 0.0001). Multivariate analysis revealed that the factors increasing the risk of death in MINOCA are as follows: older age, low eGFR, higher creatinine concentration, low left ventricular ejection fraction, and ST elevation in ECG. Conclusion Impaired kidney function is diagnosed in every third patient with MINOCA. Early and late prognosis of patents with MINOCA and renal dysfunction is poor, and their 3-year mortality is comparable to patients with myocardial infarction with significant stenosis of the coronary arteries and impaired kidney function.


Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Jozef Bartunek ◽  
Marc Vanderheyden ◽  
Bart Vandekerckhove ◽  
Samer Mansour ◽  
Bernard De Bruyne ◽  
...  

Background— Bone marrow CD133-postive (CD133 + ) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133 + progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results— Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133 + progenitor cells (12.6±2.2×10 6 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P <0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P =NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P <0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P =NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P <0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P =NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18 fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% ( P <0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion— In patients with recent myocardial infarction, intracoronary administration of enriched CD133 + cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.


2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Cheuk-Kwan Sun ◽  
Yen-Yi Zhen ◽  
Hung-I Lu ◽  
Pei-Hsun Sung ◽  
Li-Teh Chang ◽  
...  

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.


2016 ◽  
Vol 1 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Sorin Pop ◽  
Roxana Hodaş ◽  
Edvin Benedek ◽  
Diana Opincariu ◽  
Nora Rat ◽  
...  

AbstractBackground:The acute loss of myocardium, following an acute myocardial infarction (AMI) leads to an abrupt increase in the loading conditions that induces a pattern of left ventricular remodeling (LVR). It has been shown that remodeling occurs rapidly and progressively within weeks after the AMI.Study aim:The aim of our study was to identify predictors for LVR, and find correlations between them and the cardiovascular (CV) risk factors that lead to remodeling.Material and methods:One hundred and five AMI patients who underwent primary PCI were included in the study. A 2-D echocardiography was performed at baseline (day 1 ± 3 post-MI) and at 6 months follow-up. The LV remodeling index (RI), was defined as the difference between the Left Ventricular End-Diastolic diameter (LVEDD) at 6 months and at baseline. The patients were divided into 2 groups, according to the RI: Group 1 – RI >15% with positive remodeling (n = 23); Group 2 – RI ≤15% with no remodeling (n = 82).Results:The mean age was 63.26 ± 2.084 years for Group 1 and 59.72 ± 1.267 years for Group 2. The most significant predictor of LVR was the female gender (Group 1 – 52% vs. Group 2 – 18%, p <0.0001). Men younger than 50 years showed a lower rate of LVR (Group1 – 9% vs. Group 2 – 20%, p = 0.0432). In women, age over 65 years was a significant predictor for LVR (Group 1 – 26% vs. Group 2 – 9%, p = 0.0025). The CV risk factors associated with LVR were: smoking (p = 0.0008); obesity (p = 0.013); dyslipidemia (p = 0.1184). The positive remodeling group had a higher rate of LAD stenosis compared to the no-remodeling group (48% vs. 26%, p = 0.002). The presence of multi-vessel disease was shown to be higher in Group 1 (26% vs. 9%, p = 0.0025). The echocardiographic parameters that predicted LVR were: LVEF <45% (p = 0.048), mitral regurgitation (p = 0.022), and interventricular septum hypertrophy (p <0.0001).Conclusions:The CV risk factors correlated with LVR were smoking, obesity and dyslipidemia. A >50% stenosis in the LAD and the presence of multi-vessel CAD were found to be significant predictors for LVR. The most powerful predictors of LVR following AMI were: LVEF <45%, mitral regurgitation, and interventricular septum hypertrophy.


2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Selma Kenar Tiryakioglu ◽  
Hakan Ozkan ◽  
Hasan Ari ◽  
Kıvanc Yalin ◽  
Senol Coskun ◽  
...  

Background. The aim of this study is to show whether the septalE/(E′×S′)ratio assessed by tissue Doppler echocardiography can predict left ventricular remodeling after first ST segment elevation myocardial infarction treated successfully with primary percutaneous intervention.Methods. Consecutive patients (n=111) presenting with acute anterior myocardial infarction for the first time in their life were enrolled. All patients underwent successful primary percutaneous coronary intervention. Standard and tissue Doppler echocardiography were performed in the first 24-36 hours of admission. Echocardiographic examination was repeated after 6 months to reassess left ventricular volumes. SeptalE/(E′×S′)ratio was assessed by pulsed Doppler echocardiography.Results. Group 1 consisted of 33 patients with left ventricular (LV) remodeling, and Group 2 had 78 patients without LV remodeling.E/(E′×S′)was significantly higher in Group 1 (4.1±1.9versus1.65±1.32,p=0.001). The optimal cutoff value forE/(E′×S′)ratio was 2.34 with 87.0% sensitivity and 82.1% specificity.Conclusion. SeptalE/(E′×S′)values measured after the acute anterior myocardial infarction can strongly predict LV remodeling in the 6-month follow-up. In the risk assessment, the septalE/(E′×S′)can be evaluated together with the conventional echocardiographic techniques.


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