scholarly journals Qiliqiangxin Capsule Improves Cardiac Function and Attenuates Cardiac Remodeling by Upregulating miR-133a after Myocardial Infarction in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Huiyang Chen ◽  
Lixia Lou ◽  
Dongmei Zhang ◽  
Yizhou Zhao ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Control Group ◽  
Intragastric Administration ◽  
Model Group ◽  
Apoptosis Index ◽  
Cardiac Hemodynamics

Qiliqiangxin capsule (QLC), a natural herb recipe with therapeutic effect from China, has been widely used in clinical practice for attenuating cardiac remodeling induced by myocardial infarction (MI). However, the pharmacological mechanism of QLC on cardiac remodeling after MI is not entirely clear. The present study aims to investigate the effectiveness and mechanisms of QLC on cardiac remodeling induced by MI in rats. The animal model was established by permanently ligating the left anterior descending coronary artery in rats. Subsequently, rats with successful ligation were randomly divided into model group, captopril group, and QLC group. And the control group was operated upon in parallel except ligation, namely, the sham group. All rats were treated through the intragastric administration once a day for 4 weeks. Cardiac hemodynamics was measured after treatment. Then, the left ventricular mass index (LVMI) was examined. The pathological changes were observed by HE staining. The collagen volume fraction (CVF) was detected by Masson trichrome staining. The apoptosis index was obtained by TUNEL fluorescent staining. The miR-133a and mRNA of TGF-β1, CTGF, Caspase9, and Caspase3 were examined by real-time PCR. The protein expressions of TGF-β1, CTGF, Caspase9, Caspase3, and cleaved-Caspase3 were tested by Western blot. Compared with the model group, QLC partially improved cardiac hemodynamics and decreased LVMI. miR-133a was significantly increased in QLC group. In addition, QLC declined CVF by downregulating TGF-β1 rather than CTGF. Meanwhile, QLC decreased the apoptosis index by attenuating Caspase9, Caspase3, and cleaved-Caspase3. This study suggested that QLC could improve cardiac function and partially attenuate cardiac remodeling by attenuating fibrosis and decreasing apoptosis, which might be partially related to miR-133a, TGF-β1, Caspase9, and Caspase3.

scholarly journals Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway

2018 ◽  
Vol 46 (6) ◽  
pp. 2371-2385 ◽  
Author(s):  
Yu Shi ◽  
Weihong Yan ◽  
Qiaoyan Lin ◽  
Weimin Wang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Systolic Function ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Control Group ◽  
Type I ◽  
Model Group ◽  
Apoptosis Rate ◽  
Myocardial Apoptosis

Objective We investigated the protective effect of icariin on myocardial infarction-induced cardiac remodeling. Methods A cardiac remodeling model was constructed by ligating rats’ coronary artery. Different icariin and CD147 concentrations were administered in the model group, and echocardiography was used to detect systolic function, screening out ideal experimental concentrations. The ventricular systolic function, myocardial apoptosis rate, and expression of collagen type I (Col I), Col III, CD147, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by hematoxylin–eosin staining, TUNEL assay, and western blot. MMP-9 activity was evaluated by gelatin zymography. Results The expression of Col I, Col III, CD147, and MMP-9 was higher, the expression of TIMP-1 was lower, and the maximal rates of left ventricular pressure rise and fall (+dp/dtmax and −dp/dtmax, respectively) were lower in model than control rats. The expression of CD147, MMP-9, Col I, and Col III was lower, the expression of TIMP-1 was higher, and the +dp/dtmax and −dp/dtmax were higher in the icariin than model group. The apoptosis rate was lower in the icariin and icariin + CD147 groups than control group. Conclusion Icariin attenuated myocardial apoptosis following myocardial infarction by apoptosis rate reduction and CD147/MMP-9 pathway inhibition.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

scholarly journals Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction

2014 ◽  
Vol 307 (5) ◽  
pp. H741-H751 ◽  
Author(s):  
Hongmei Peng ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Xiangguo Dai ◽  
Edward L. Peterson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cell Survival ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cardiac Rupture ◽  
Gelatinolytic Activity ◽  
P53 Expression

Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg−1·day−1 ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

scholarly journals HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

2020 ◽  
Author(s):  
Chong Du ◽  
Xiao-Wen Chen ◽  
Ze-Mu Wang ◽  
Hao-Yu Meng ◽  
Ya-Fei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Cardiac Function ◽  
Infarct Size ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Cardiac Repair ◽  
Control Group ◽  
Hepatocyte Growth ◽  
Better Than

Abstract Background: Previous studies reported that hepatocyte growth factor (HGF) could promote angiogenesis and cardiac function after myocardial infarction (MI) in pigs. However, the results of these studies were controversial. To clarify the therapeutic efficacy of local HGF administration after MI, we performed a systematic review and meta-analysis of data from the pig models, which could provide evidence for the feasibility of clinical HGF application.Methods: PubMed, EMBASE, and China National Knowledge Infrastructure were searched for randomized studies that correspond to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The primary endpoint indicators were identified as the left ventricular ejection fraction (LVEF) and capillaries density. Other parameters reflecting cardiac function and ventricular remodeling were analyzed as secondary indicators, including ventricular volume, infarct size, apoptotic index and others.Results: In total, 9 studies were finally included in the meta-analysis. On comparing the cardiac function indexes, the HGF group was found to be better than the control group in regard to LVEF, stroke volume, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). However, no statistically significant differences were found in heart rate. Furthermore, HGF treatment promotes angiogenesis in ischemic areas, which is manifested by increased capillary density. In addition, the HGF group was found to be better than the control group when it comes to infarct size, arteriole densities, and other indicators of cardiac remodeling.Conclusions: HGF treatment can effectively promote cardiac function and cardiac repair including angiogenesis, and this strategy is a promising cardio-protective approach that merits further clinical studies.

Blockade of NF-κB improves cardiac function and survival after myocardial infarction

2006 ◽  
Vol 291 (3) ◽  
pp. H1337-H1344 ◽  
Author(s):  
Shunichi Kawano ◽  
Toru Kubota ◽  
Yoshiya Monden ◽  
Takaki Tsutsumi ◽  
Takahiro Inoue ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Targeted Disruption ◽  
Ventricular Rupture ◽  
Inflammatory Processes

NF-κB is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-κB ameliorates cardiac remodeling and failure after myocardial infarction (MI). Knockout mice with targeted disruption of the p50 subunit of NF-κB (KO) were used to block the activation of NF-κB. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-κB was activated in noninfarct as well as infarct myocardium in WT + MI mice, while the activity was completely abolished in KO mice. Blockade of NF-κB significantly reduced early ventricular rupture after MI and improved survival by ameliorating congestive heart failure. Echocardiographic and pressure measurements revealed that left ventricular fractional shortening and maximum rate of rise of left ventricular pressure were significantly increased and end-diastolic pressure was significantly decreased in KO + MI mice compared with WT + MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in the noninfarct myocardium of KO + MI mice. Blockade of NF-κB did not ameliorate expression of proinflammatory cytokines in infarct or noninfarct myocardium. In contrast, phosphorylation of c-Jun NH2-terminal kinase was almost completely abolished in KO + MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-κB reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-κB might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.

scholarly journals Elastin Stabilizes an Infarct and Preserves Ventricular Function

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Tomohiro Mizuno ◽  
Terrence M. Yau ◽  
Richard D. Weisel ◽  
Chris G. Kiani ◽  
Ren-Ke Li
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Left Ventricular ◽  
Myocardial Scar ◽  
Elastic Fibers ◽  
Control Group ◽  
Lv Function ◽  
Infarct Region ◽  
Lv Volume

Background— After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. Methods and Results— A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2×10 6 syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller ( P <0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better ( P <0.05) in the elastin group than in the control group. Conclusions— Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling

2015 ◽  
Vol 309 (1) ◽  
pp. H213-H221 ◽  
Author(s):  
Atsushi Ogino ◽  
Genzou Takemura ◽  
Ayako Hashimoto ◽  
Hiromitsu Kanamori ◽  
Hideshi Okada ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Proliferating Cells ◽  
Angiogenic Activity ◽  
Adrenergic Antagonist ◽  
Peripheral Vasodilator

Although OPC-28326, 4-( N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice ( n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Cheng ◽  
X Y Song ◽  
L Chen ◽  
R D Xu ◽  
Q Qin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Conditioned Medium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effect

Abstract Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210 Background A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes. Purpose The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210. Methods and results The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling. Conclusion Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia. Acknowledgement/Funding National Natural Science Foundation of China (Grant Nos. 81470467)

Abstract 302: Cathepsin D Haploinsufficiency Exacerbates Post Myocardial Infarction Cardiac Remodeling and Malfunction by Impairing Autophagosome Removal

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Penglong Wu ◽  
Wei Zhu ◽  
Jingbo Li ◽  
Xuejun “XJ” Wang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Cathepsin D ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Control Group ◽  
Autophagic Flux ◽  
Protein Levels ◽  
Lysosomal Protease ◽  
The Impact

Background: A marked decrease in the protein level and activity of cathepsin D (Ctsd), a major lysosomal protease, has been observed in failing human hearts; however, the pathophysiological significance of Ctsd downregulation in the heart remains undefined. Given the increasingly recognized role of the autophagic-lysosomal pathway in cardiac pathobiology, we sought to determine the impact of Ctsd haploinsufficiency on post myocardial infarction (MI) cardiac remodeling and explore the underlying mechanism. Methods and Results: MI was induced in 2-3 months old mixed-sex wild type (WT) or heterozygous Ctsd knockout (Ctsd +/- ) mice via permanent ligation of the left anterior descending (LAD) coronary artery. Myocardial Ctsd protein levels are reduced by ~50% in Ctsd +/- mice, compared with WT mice. Echocardiography (Echo) did not detect discernible difference between Ctsd +/- and WT mice immediately before and 1 week (wk) after MI; however, compared with the WT MI group, significantly greater left ventricular (LV) internal diameters at end systole and at end diastole and significantly smaller ejection fraction and fractional shortening were detected in the Ctsd +/- MI group at 2, 3, and 4 wks post-MI (p<0.05 ~ 0.001). LV pressure-volume relationship analyses at 4 wks post-MI also revealed that LV maximum and minimum dP/dt values were significantly reduced in the WT MI group, compared with the WT sham control group (p<0.05, 0.01); these post-MI reductions were more pronounced in the Ctsd +/- MI group (P<0.05, 0.01). The infarct size at 4 wks post-MI measured with trichrome staining was significantly enlarged by Ctsd +/- (p<0.002). These results indicate that Ctsd haploinsufficiency exacerbates post-MI cardiac remodeling and malfunction. Post-MI myocardial Ctsd protein levels were increased in WT mice but this increase was not detectable in Ctsd +/- mice. However, the myocardial protein levels of LC3-II, beclin1, and Atg5 were further elevated in Ctsd +/- MI mice, compared with the WT MI mice, indicative of impairment of autophagic flux in Ctsd +/- MI mice. Conclusion: Ctsd haploinsufficiency exacerbates maladaptive post-MI cardiac remodeling and malfunction likely through impairing autophagosome removal.

P6298Pericardial transplantation of adipose-derived stromal cells with self-assembling peptides scaffold prevents cardiac remodeling after myocardial infarction in mice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Kondo ◽  
T Nagai ◽  
I Aoki ◽  
M Kanda ◽  
T Takahashi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Stromal Cells ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Scar Area ◽  
Self Assembling ◽  
Adipose Derived Stromal Cells ◽  
Donor Cells ◽  
Ventricular Wall Thickness

Abstract Introduction and purpose Cardiac cell therapy to patients with heart failure after myocardial infarction (MI), has shown little improvement in cardiac function. The rate of engraftment after cell transplantation (TX) to the ischemic heart is low because of the leakage of transplanted cells without scaffold, the friction between the graft and thorax, and poor vascularization to the graft. We created a novel TX method (Figure 1) to transplant adipose-derived stromal cells (ASCs) with scaffold into the pericardial space where the pericardium protected the graft. We evaluated the therapeutic efficacy of pericardial TX of ASCs on the cardiac function and remodeling after MI. Methods We isolated ASCs from the brown adipose tissue of donor mice (C57BL6-Tg (CAG-EGFP), five weeks). ASCs increased and differentiated into spontaneously beating myocytes, endothelial cells, and pericytes three weeks after ex vivo culture. Cells were trypsinized and mixed with self-assembling peptides scaffold. Each graft (100μl gel scaffold) had 1×106 ASCs. To make recipient MI mice (C57BL6, 12 weeks), we ligated the left coronary artery through small chest incision without cutting rib bone to avoid postoperative adhesions. We confirmed the deterioration of cardiac function by echocardiography (n=21) and MRI (n=4) three weeks after MI. Then, recipient MI mice had TX (syngeneic, no immunosuppression). We opened the pericardium and transplanted the graft into the pericardial space. By suturing the pericardium, the graft was fixed on the MI scar area (Figure 1). We labeled donor cells with GFP and the scaffold with biotin. We evaluated cardiac function of TX group (n=10) and control group (MI with sham TX, n=11) by echocardiography. Results In the scaffold, donor cells increased three days to two weeks after TX, and slightly decreased four weeks after TX. The graft thickness was 0.9±0.2mm (two weeks after TX) and 0.7±0.2mm (four weeks after TX). There were many vWF positive vessels in the scaffold and some of which were GFP positive. Echocardiography showed that left ventricular diastolic dimension (LVDd) of TX group, did not increase four weeks after TX (ΔLVDd = −0.02mm, P=0.80). While, LVDd of control group significantly increased (ΔLVDd = +0.23mm, P=0.02) due to cardiac remodeling after MI. MRI confirmed the increase in left ventricular wall thickness in the MI scar area up to 4 weeks in TX group (n=2). Conclusions Pericardial transplantation of ASCs prevents cardiac remodeling. Its beneficial effect might be mediated by improved rate of engraftment, neovascularization, and increased ventricular wall thickness in the MI scar area. Acknowledgement/Funding Grants-in-Aid for Scientific Research

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