Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction
Abstract Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myoca...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-06-01
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| Series: | Cell Regeneration |
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| Online Access: | https://doi.org/10.1186/s13619-022-00121-y |
| _version_ | 1828820861193289728 |
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| author | Xing Qin Juanjuan Fei Yu Duan Asli F. Ceylan Fuyang Zhang Jun Ren |
| author_facet | Xing Qin Juanjuan Fei Yu Duan Asli F. Ceylan Fuyang Zhang Jun Ren |
| author_sort | Xing Qin |
| collection | DOAJ |
| description | Abstract Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation. |
| first_indexed | 2024-12-12T12:41:28Z |
| format | Article |
| id | doaj.art-30ab90ef8e4f412a8c9dccf191d0ad6e |
| institution | Directory Open Access Journal |
| issn | 2045-9769 |
| language | English |
| last_indexed | 2024-12-12T12:41:28Z |
| publishDate | 2022-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Cell Regeneration |
| spelling | doaj.art-30ab90ef8e4f412a8c9dccf191d0ad6e2022-12-22T00:24:12ZengSpringerOpenCell Regeneration2045-97692022-06-0111111110.1186/s13619-022-00121-yBeclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarctionXing Qin0Juanjuan Fei1Yu Duan2Asli F. Ceylan3Fuyang Zhang4Jun Ren5Department of Cardiology, Xijing Hospital, Fourth Military Medical UniversityDepartment of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan UniversityDepartment of Cardiology, Xijing Hospital, Fourth Military Medical UniversityDepartment of Medical Pharmacology, Ankara Yildirim Beyazit University, Faculty of MedicineDepartment of Cardiology, Xijing Hospital, Fourth Military Medical UniversityDepartment of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan UniversityAbstract Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.https://doi.org/10.1186/s13619-022-00121-yMyocardial infarctionMSCsBeclin1ContractionApoptosisAutophagy |
| spellingShingle | Xing Qin Juanjuan Fei Yu Duan Asli F. Ceylan Fuyang Zhang Jun Ren Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction Cell Regeneration Myocardial infarction MSCs Beclin1 Contraction Apoptosis Autophagy |
| title | Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction |
| title_full | Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction |
| title_fullStr | Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction |
| title_full_unstemmed | Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction |
| title_short | Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction |
| title_sort | beclin1 haploinsufficiency compromises mesenchymal stem cell offered cardioprotection against myocardial infarction |
| topic | Myocardial infarction MSCs Beclin1 Contraction Apoptosis Autophagy |
| url | https://doi.org/10.1186/s13619-022-00121-y |
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