Dataset Information

Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages.

ABSTRACT: Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (M?) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery. Hence, zwitterionic biodegradable copolymer poly(lactide)-polycarboxybetaine (PLA-PCB, PP), companied with PS, was used to provide a good colloidal stability and long blood circulation for the nanocubes. Given the above, a theranostic nanosystem (PP/PS@MIONs) was constructed for early treatment of MI. With external magnetic field-induced targeting and PS targeting, the nanosystem enhanced the accumulation in infarcted area, and accelerated the resolution of early inflammatory responses. Moreover, the nanocubes in system were promoted to escape from endosomes/lysosomes via protonation of PCB, which contributes to accurate MRI. This nanosystem showed good inflammation-resolving effects and imaging ability in MI model rats. Therefore, this theranostic nanosystem can realize accurate visualization and significantly improve the treatment efficacy of MI at early stage.

SUBMITTER: Chen J

PROVIDER: S-EPMC5695003 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages.

Chen Jingli J Yang Jun J Liu Ruiyuan R Qiao Chenmeng C Lu Zhiguo Z Shi Yuanjie Y Fan Zhanming Z Zhang Zhenzhong Z Zhang Xin X

Theranostics 20170926 17

Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic reso ...[more]

PMID: 29158816

Similar Datasets

Project description:An innovative approach for cardiac regeneration following injury is to induce endogenous cardiomyocyte (CM) cell cycle re-entry. In the present study, CMs from adult rat hearts were isolated and transfected with cel-miR-67 (control) and rno-miR-210. A significant increase in CM proliferation and mono-nucleation were observed in miR-210 group, in addition to a reduction in CM size, multi-nucleation, and cell death. When compared to control, ?-catenin and Bcl-2 were upregulated while APC (adenomatous polyposis coli), p16, and caspase-3 were downregulated in miR-210 group. In silico analysis predicted cell cycle inhibitor, APC, as a direct target of miR-210 in rodents. Moreover, compared to control, a significant increase in CM survival and proliferation were observed with siRNA-mediated inhibition of APC. Furthermore, miR-210 overexpressing C57BL/6 mice (210-TG) were used for short-term ischemia/reperfusion study, revealing smaller cell size, increased mono-nucleation, decreased multi-nucleation, and increased CM proliferation in 210-TG hearts in contrast to wild-type (NTG). Likewise, myocardial infarction (MI) was created in adult mice, echocardiography was performed, and the hearts were harvested for immunohistochemistry and molecular studies. Compared to NTG, 210-TG hearts showed a significant increase in CM proliferation, reduced apoptosis, upregulated angiogenesis, reduced infarct size, and overall improvement in cardiac function following MI. ?-catenin, Bcl-2, and VEGF (vascular endothelial growth factor) were upregulated while APC, p16, and caspase-3 were downregulated in 210-TG hearts. Overall, constitutive overexpression of miR-210 rescues heart function following cardiac injury in adult mice via promoting CM proliferation, cell survival, and angiogenesis. KEY MESSAGES:MiRNA-210 transfected adult rat CMs show proliferation and reduced cell death in vitro. Cell cycle inhibitor APC is a target of miR-210. MiR-210 overexpressing (210-TG) mouse hearts show CMs cell cycle re-entry and survival post myocardial injury. 210-TG mice show significant neovascularization and angiogenic potential post myocardial infarction. 210-TG hearts show reduced infarct size following ischemic injury.

Project description:Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Dataset Information

Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages.

Publications

Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair <i>via</i> Modulation of Macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets