Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

Chen, Gangbin; Li, Yang; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

doi:10.1038/srep30643

Cited by 31 publications

(27 citation statements)

References 40 publications

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“…The infarct and fibrotic area was evaluated as previously described. 18 , 20 , 23 After MI (14 and 60 days), hearts were cut into six sections and incubated in 1% triphenyl tetrazolium chloride (TTC) for 10 min at room temperature (white indicates infarct area; red indicates normal myocardium). Infarct areas were measured digitally using Image-Pro Plus 6.0 (Media Cybernetics, Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration

Wang

et al. 2018

Cardiovascular Research

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AimsLong noncoding RNAs (lncRNAs) are critical regulators of cardiovascular lineage commitment and heart wall development, but their roles in regulating endogenous cardiac regeneration are unclear. The present study investigated the role of human-derived lncRNA in regulating endogenous cardiac regeneration as well as the underlying mechanisms.Methods and resultsWe compared RNA sequencing data from human foetal and adult hearts and identified a novel lncRNA that was upregulated in adult hearts (Genesymbol NONHSAG000971/NONHSAT002258 or ENST00000497710.5), which was a splice variant of the AZIN2 gene (AZIN2-sv). We used quantitative PCR to confirm the increased expression of AZIN2-sv in adult rat hearts. Coexpression network analysis indicated that AZIN2-sv could regulate proliferation. Loss- and gain-of-function approaches demonstrated that AZIN2-sv negatively regulated endogenous cardiomyocyte proliferation in vitro and in vivo. Knockdown of AZIN2-sv attenuated ventricular remodelling and improved cardiac function after myocardial infarction. Phosphatase and tensin homolog (PTEN) was identified as a target of AZIN2-sv, their direct binding increased PTEN stability. Furthermore, AZIN2-sv acted as a microRNA-214 sponge to release PTEN, which blocked activation of the PI3 kinase/Akt pathway to inhibit cardiomyocyte proliferation.ConclusionsThe newly discovered AZIN2-sv suppressed endogenous cardiac regeneration by targeting the PTEN/Akt pathway. Thus, AZIN2-sv may be a novel therapeutic target for preventing and treating heart failure.

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Section: Methodsmentioning

confidence: 99%

Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration

Wang

et al. 2018

Cardiovascular Research

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“…45 Furthermore, the delivery of the metalloproteinase inhibitor 3 gene to the infarct region could be enhanced by using gene carrying microbubbles decorated with a matrix metalloproteinase 2 antibody, which improved cardiac function and reduced the infarct region. 19 Next to loading the microbubble shell with pharmaceutical agents and genes, the gas core can be partially replaced by therapeutic gases like hydrogen 46 or hydrogen sulfide, 47 two gases that are used to protect myocytes after myocardial ischemia-reperfusion injury. It was shown that targeted microbubble destruction substantially increased the local gas concentration and reduced the damaged tissue area after myocardial infarctions.…”

Section: Therapeutic Ceus In Cardiovascular Applicationsmentioning

confidence: 99%

“…It was shown that targeted microbubble destruction substantially increased the local gas concentration and reduced the damaged tissue area after myocardial infarctions. 46,47 Despite the significant potential of CEUS-based therapies, there is still a need to optimize treatment parameters, as many adverse events, like microvascular leakage, intracardiac hemolysis, capillary rupture, or inflammatory cell infiltration have been described in rodents. 23…”

Section: Therapeutic Ceus In Cardiovascular Applicationsmentioning

confidence: 99%

Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases

Rix

Curaj

Liehn

et al. 2019

Semin Thromb Hemost

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Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-mode and functional M-, pulsed-wave- and Doppler mode, which have their limitations in both precise cardiac chambers' delineation and small vessel imaging. The introduction of contrast-enhanced US, employing microbubble suspensions as contrast agent, has enabled a better delineation of heart chambers, the visualization of myocardial microvasculature, and the atherosclerotic plaque neovascularization. Moreover, specific disease-related molecular tracers have been developed by modifying the microbubbles with targeting ligands directed to biological markers exposed to the luminal side of the blood vessels. Microbubble functionalization has enabled in vivo molecular US imaging of various stages of atherosclerosis, from plaque initiation to plaque vulnerability, and neointima formation following revascularization procedures. Furthermore, oscillating microbubbles have been used to mechanically dissolve thrombus material and may act as carriers of drugs and nucleic acids that are released locally by US pulses. This review article summarizes recent advances in functional and molecular US images and discusses therapeutic applications of microbubbles. The addressed topics include an overview on microbubble formats, microbubble detection methods, molecular targets of cardiovascular diseases, and the use of microbubbles for thrombolysis and drug delivery.

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“…The optimal ratio of H2S/C3F8 was found to be 2/2 with the highest H2S-loading capacity. US-targeted hs-MB destruction controlled myocardial infarct sizes and also preserved left ventricular functions without any influence on hemodynamics or the respiratory system, thus leading to myocardial ischemia-reperfusion injury alleviation [95]. Zhu et al tested the injection of DOX in the H22 hepatocellular carcinoma (HCC)-xenografted models combined with UTMD.…”

Section: Drug/gene Deliverymentioning

confidence: 99%

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

Wang

et al. 2016

Applied Sciences

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Microbubbles as traditional ultrasound contrast agents have seen tremendous developments and bio-applications in the past decades. Due to their outstanding performance, advanced microbubbles as a multifunctional platform combining both imaging and therapy have been increasingly attracting attention. Associated with ultrasound-mediated stimuli, targeting drug transportation with high precision can be established and, as a consequence, a synergistic treatment strategy may prevail, which implies a bright perspective for this brand-new technology. This perspective article will summarize the latest developments on the advanced microbubbles, and review their emerging biomedical applications for the vast community of both applied ultrasound and functional ultrasound-based materials.

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Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

Cited by 31 publications

References 40 publications

Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration

Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration

Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

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