Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Yang, Yun; Shi, Chunying; Hou, Xun; Zhao, Yannan; Chen, Bing; Tan, Bo; Deng, Zongwu; Li, Qingguo; Liu, Jianzhou; Xiao, Zhifeng; Miao, Qi; Dai, Jianwu

doi:10.1016/j.jconrel.2015.06.036

Cited by 48 publications

(27 citation statements)

References 38 publications

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“…31,32 Interestingly, following CDH11 blockade we observed a reduction in transcription of both Fgf2 and Vegfa1, two pro-angiogenic genes often associated with improved revascularization and better outcomes following MI. [33][34][35][36] However, we also observed more muscularized vessels -likely arterioles -in infarcted areas of SYN0012-treated hearts at 21 days after MI; this corresponds to a time when angiogenic gene expression has run its course. 37 We speculate that SYN0012 may either preserve native vasculature or hasten maturation of new vasculature, such that the hypoxic conditions which typically drive angiogenic signaling are reduced.…”

Section: Discussionmentioning

confidence: 90%

Cadherin-11 Blockade Reduces Inflammation-Driven Fibrotic Remodeling and Improves Outcomes After Myocardial Infarction

Schroer

Bersi

Clark

et al. 2019

Preprint

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Background: Over one million Americans experience myocardial infarction (MI) every year, and the resulting scar and subsequent cardiac fibrosis contribute to heart failure and death. A specialized cell-cell adhesion protein, cadherin-11 (CDH11), contributes to inflammation and fibrosis in rheumatoid arthritis, pulmonary fibrosis, and aortic valve calcification but has not yet been studied in the context of cardiac remodeling after MI. We hypothesized that targeting CDH11 function after MI would reduce inflammation-driven fibrotic remodeling and infarct expansion to improve functional outcomes in mice.Methods: MI was induced by ligation of the left anterior descending artery in transgenic mice with reduced or ablated CDH11, wild type mice receiving bone marrow transplants from Cdh11 transgenic animals, and wild type mice treated with a functional blocking antibody against CDH11 (SYN0012). Cardiac function was measured by echocardiography, expression of cell populations was quantified by flow cytometry, and tissue remodeling by altered histological assessment and transcription of inflammatory and pro-angiogenic genes by qPCR. Co-culture was used to assess interactions between cardiac fibroblasts and macrophages.

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Section: Discussionmentioning

confidence: 90%

Cadherin-11 Blockade Reduces Inflammation-Driven Fibrotic Remodeling and Improves Outcomes After Myocardial Infarction

Schroer

Bersi

Clark

et al. 2019

Preprint

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“…Interestingly, previous studies reported that the activation of ERK1 and ERK2 cascade (46) and vascular endothelial growth factor signaling pathway (47) were associated with the attenuation of I/R injury. These results showed that the application of Custodiol-supplemented with hypoxic CM-BMSCs for donor heart preservation protected graft against I/R injury via different signal pathways.…”

Section: Discussionmentioning

confidence: 99%

Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

Zhou

Liu

et al. 2020

Preprint

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Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium derived from BMSCs (CM-BMSCs) would improve post-transplant graft function. Methods: Normoxic CM and hypoxic CM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CM (N-CM), or hypoxic CM (H-CM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic CM and normoxic CM.Results: After heart transplantation, the donor heart preservation with normoxic CM was associated with shorter re-beating time, histopathological scores, and left ventricular systolic diameter, higher ejection fraction, and fractional shortening of transplanted hearts. These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CM compared with normoxic CM. Furthermore, compared with vehicle and N-CM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CM group. Conclusions: Our results indicate that cardioplegic solution-enriched with hypoxic CM-BMSCs can be a novel and promising preservation solution for donor hearts.

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“…Втім цей фактор є дуже важливим у забезпеченні неореваскуляризації періінфарктної та інфарктної зони та веде до покращення скоротливої функції ЛШ після інфаркту міокарда [18]. У багатьох експериментальних роботах була показана ефективність застосування VEGF в терапії ГІМ [19,20]. СРБ не тільки є типовим білком гострої фази запалення, але й має самостійне патогенетичне значення в процесах атерогенезу, дестабілізації коронарного атеросклерозу та тромбоутворення.…”

Section: ðåçóëüòàòèunclassified

Вплив Терапії Внутрішньовенним Інгібітором 5-Ліпоксигенази Кверцетином На Функцію Ендотелію, Вираженість Системного Запалення Та Прооксидантного Стресу При Гострому Інфаркті Міокарда З Елевацією ST

Lutai¹,

Parkhomeko²,

Ryzhkova³

et al. 2022

ЕМ

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Ефективність інгібітору 5-ліпоксигенази кверцетину у пацієнтів із гострим інфарктом міокарда (ГІМ), яким з метою реперфузії вводили тромболітичні препарати, була доведена на початку 2000-х років. Застосування препарату дозволяло суттєво обмежити зону некротизованого міокарда та зменшити кількість клінічних ускладнень як протягом госпітального періоду, так і за результатами трива-Îðèãèíàëüíûå èññëåäîâàíèÿ Original Researches лого спостереження у цієї категорії хворих [1, 2]. Це дозволило зареєструвати кверцетин для лікування

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Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Cited by 48 publications

References 38 publications

Cadherin-11 Blockade Reduces Inflammation-Driven Fibrotic Remodeling and Improves Outcomes After Myocardial Infarction

Cadherin-11 Blockade Reduces Inflammation-Driven Fibrotic Remodeling and Improves Outcomes After Myocardial Infarction

Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

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