Non-invasive contrast enhanced ultrasound molecular imaging of inflammation in autoimmune myocarditis for prediction of left ventricular fibrosis and remodeling

Steinl, David C.; Xu, Liangliang; Ochoa-Espinosa, Amanda; Punjabi, Mukesh; Kaufmann, Beat A.

doi:10.1371/journal.pone.0224377

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…For binary mixtures, the components were generally dissolved and premixed in organic solvent first, then dried to form a lipid film, and dispersed in aqueous medium before microbubbles were produced ,, (i.e., indirect method). For ternary mixtures, the components were generally dispersed directly in aqueous medium before microbubble production ,− (i.e., direct method). Based on the effect of cooling rate on microstructures in large microbubbles (>10 μm) after microbubble production, we hypothesize that the method of handling the lipids prior to microbubble production may also influence the ligand distribution and/or lipid phase in the coating of microbubbles.…”

Section: Introductionmentioning

confidence: 99%

Ligand Distribution and Lipid Phase Behavior in Phospholipid-Coated Microbubbles and Monolayers

et al. 2020

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Phospholipid-coated targeted microbubbles are ultrasound contrast agents that can be used for molecular imaging and enhanced drug delivery. However, a better understanding is needed of their targeting capabilities and how they relate to microstructures in the microbubble coating. Here, we investigated the ligand distribution, lipid phase behavior, and their correlation in targeted microbubbles of clinically relevant sizes, coated with a ternary mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), with PEG40-stearate and DSPE-PEG2000. To investigate the effect of lipid handling prior to microbubble production in DSPC-based microbubbles, the components were either dispersed in aqueous medium (direct method) or first dissolved and mixed in an organic solvent (indirect method). To determine the lipid-phase behavior of all components, experiments were conducted on monolayers at the air/water interface. In comparison to pure DSPC and DPPC, the ternary mixtures had an additional transition plateau around 10–12 mN/m. As confirmed by infrared reflection absorption spectroscopy (IRRAS), this plateau was due to a transition in the conformation of the PEGylated components (mushroom to brush). While the condensed phase domains had a different morphology in the ternary DPPC and DSPC monolayers on the Langmuir trough, the domain morphology was similar in the coating of both ternary DPPC and DSPC microbubbles (1.5–8 μm diameter). The ternary DPPC microbubbles had a homogenous ligand distribution and significantly less liquid condensed (LC) phase area in their coating than the DSPC-based microbubbles. For ternary DSPC microbubbles, the ligand distribution and LC phase area in the coating depended on the lipid handling. The direct method resulted in a heterogeneous ligand distribution, less LC phase area than the indirect method, and the ligand colocalizing with the liquid expanded (LE) phase area. The indirect method resulted in a homogenous ligand distribution with the largest LC phase area. In conclusion, lipid handling prior to microbubble production is of importance for a ternary mixture of DSPC, PEG40-stearate, and DSPE-PEG2000.

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Section: Introductionmentioning

confidence: 99%

Ligand Distribution and Lipid Phase Behavior in Phospholipid-Coated Microbubbles and Monolayers

et al. 2020

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“…Myocardial fibrosis is a typical characteristic observed during the transition of myocarditis to DCM ( 43 ). A previous study reported the contribution of Smad-dependent signaling pathways to TGF-β-induced cardiac fibrosis ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis

Wang

Cao

et al. 2022

Exp Ther Med

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Spironolactone improves cardiac structure, function and prognosis in patients with heart failure and delays the progression of cardiac fibrosis. However, the exact underlying mechanism of this process remains to be elucidated. The present study therefore aimed to explore the protective effect and underlying mechanism of the aldosterone receptor antagonist, spironolactone, on myocardial fibrosis in mice with experimental autoimmune myocarditis (EAM). The EAM model was induced in BALB/c mice via immunization with murine cardiac α-myosin heavy chain sequence polypeptides. The cardiac function of the mice was assessed using echocardiography and the levels of inflammatory cytokines were quantified using ELISA. E26 transformation-specific sequence-1 (Ets-1) expression was knocked down using lentivirus-mediated small interference RNA. Total collagen deposition was assessed using Masson's trichrome and Ets-1, TGF-β1, Smad2/3, collagen I and III protein expression levels were detected using immunohistochemistry and western blotting. MMP-2 and MMP-9 mRNA expression levels and activity was determined using reverse transcription-quantitative PCR and gelatin zymography, respectively. The results of the present study demonstrated that spironolactone significantly improved myocardium hypertrophy, diastolic cardiac function and decreased myocardial inflammation and collagen deposition induced by EAM. Spironolactone treatment significantly inhibited Ets-1 and smad2/3 phosphorylation. In addition, inhibition of Ets-1 reduced the expression and activity of MMP-2 and MMP-9 and decreased cardiac fibrosis in EAM mice. The results indicated that the improvement of myocardial fibrosis by spironolactone may be associated with the TGF-β1/Smad-2/3/Ets-1 signaling pathway in EAM mice.

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“…Experimental autoimmune myocarditis (EAM) animal models largely mimic pathological cardiac damage caused by acute-onset myocarditis in humans. [32][33][34] Therefore, EAM mice on day 21 of immunization were selected for subsequent studies. Therefore, multimodal imaging (US/CMR/PA imaging) is highly desirable (Fig.…”

Section: Introductionmentioning

confidence: 99%

Macrophage membrane-modified targeted phase-change nanoparticles for multimodal imaging of experimental autoimmune myocarditis

Yin,

Zheng,

Zhang

et al. 2024

Nanoscale

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Non-invasive contrast enhanced ultrasound molecular imaging of inflammation in autoimmune myocarditis for prediction of left ventricular fibrosis and remodeling

Cited by 9 publications

References 14 publications

Ligand Distribution and Lipid Phase Behavior in Phospholipid-Coated Microbubbles and Monolayers

Ligand Distribution and Lipid Phase Behavior in Phospholipid-Coated Microbubbles and Monolayers

Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis

Macrophage membrane-modified targeted phase-change nanoparticles for multimodal imaging of experimental autoimmune myocarditis

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