EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction

Cuadrado, Irene; Piedras, Maria J.; Herruzo, Irene; Turpin, María del Carmen; Castejón, Borja; Reventún, Paula; Martín, Ana María Pérez; Saura, Marta; Zamorano, José Luís; Zaragoza, Carlos

doi:10.7150/thno.13352

Cited by 47 publications

(59 citation statements)

References 36 publications

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“…Histology. LV sections were fixed in a 10% formalin solution, dehydrated in ethanol, and then embedded in paraffin as previously described 36 . Tissue sections (5 μm) were obtained in a microtome, were deparaffinized, rehydrated, and stained with Masson's trichrome staining kit (EMD Millipore Corporation, Billerica, MA, USA) and Sirius red staining (Sigma-Aldrich, San Luis, MI, USA) for fibrosis quantification.…”

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confidence: 99%

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

Reventún¹,

Sánchez-Esteban²,

Cook³

et al. 2020

Sci Rep

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Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.

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confidence: 99%

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

Reventún¹,

Sánchez-Esteban²,

Cook³

et al. 2020

Sci Rep

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“…Infarct size was a critical parameter of the cardiac function 17 . The infarct sizes of different groups were also examined by the immunohistochemical and morphometric analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Lewis rats were used to conduct a randomized and blinded study. One group (n=8-11) was given a sham surgery while other four groups (n=8-11) underwent MI via permanent ligation of the left descending artery 17 . The animal studies were performed in accordance with the institutional ethics committee regulations and guidelines on animal welfare.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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 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.

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“…the imaging of multiple MNP types simultaneously. In the new field of theranostics, a combination of particle types is envisioned that allows diagnosis followed by treatment in one experiment, such as the combined tracking of stem cells/drugs, therapy, the monitoring of disease progress and adequate response (Cuadrado et al 2016, Zheng et al 2016, or the specific targeting of cancer with MNP types suitable for imaging, drug targeting and thermoablation (Li 2014). Also, from the future perspective of personalized nanomedicine, in which the medicine is tailored to the needs of the patient, research needs to be done to investigate what size, properties and composition the MNPs should have in order to treat an individual patient in the most effective way, so inter-individual variability in the therapeutic response can be reduced (Miller et al 2015, Tietjen andSaltzman 2015).…”

Section: Introductionmentioning

confidence: 99%

Multi-color magnetic nanoparticle imaging using magnetorelaxometry

et al. 2017

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Magnetorelaxometry (MRX) is a well-known measurement technique which allows the retrieval of magnetic nanoparticle (MNP) characteristics such as size distribution and clustering behavior. This technique also enables the non-invasive reconstruction of the spatial MNP distribution by solving an inverse problem, referred to as MRX imaging. Although MRX allows the imaging of a broad range of MNP types, little research has been done on imaging different MNP types simultaneously. Biomedical applications can benefit significantly from a measurement technique that allows the separation of the resulting measurement signal into its components originating from different MNP types. In this paper, we present a theoretical procedure and experimental validation to show the feasibility of MRX imaging in reconstructing multiple MNP types simultaneously. Because each particle type has its own characteristic MRX signal, it is possible to take this a priori information into account while solving the inverse problem. This way each particle type's signal can be separated and its spatial distribution reconstructed. By assigning a unique color code and intensity to each particle type's signal, an image can be obtained in which each spatial distribution is depicted in the resulting color and with the intensity measuring the amount of particles of that type, hence the name multi-color MNP imaging. The theoretical procedure is validated by reconstructing six phantoms, with different spatial arrangements of multiple MNP types, using MRX imaging. It is observed that MRX imaging easily allows up to four particle types to be separated simultaneously, meaning their quantitative spatial distributions can be obtained.

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EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction

Cited by 47 publications

References 36 publications

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

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

Multi-color magnetic nanoparticle imaging using magnetorelaxometry

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