Precise treatment of acute antibody-mediated cardiac allograft rejection in rats using C4d-targeted microbubbles loaded with nitric oxide
| Autor: | Xiaolong Chen, Fei Han, Jie Ren, Qiaojia Li, Tao Liao, Zhe Yang, Yannan Zhang, Tinghui Yin, Qiquan Sun, Zhengyu Huang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Graft Rejection
0301 basic medicine Pulmonary and Respiratory Medicine medicine.medical_specialty Biopsy Urology 030230 surgery Nitric Oxide Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Isoantibodies Complement C4b Animals Immunologic Factors Medicine Transplantation Microbubbles biology Cardiac allograft business.industry Therapeutic effect Ultrasound Allografts medicine.disease Thrombosis Rats Disease Models Animal 030104 developmental biology chemistry biology.protein Heart Transplantation Surgery Antibody Cardiology and Cardiovascular Medicine business Contrast-enhanced ultrasound |
| Zdroj: | The Journal of Heart and Lung Transplantation. 39:481-490 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2020.02.002 |
| Popis: | BACKGROUND Antibody-mediated rejection (AMR) constitutes an important cause of cardiac allograft loss; however, all current therapeutic strategies represent systemic applications with unsatisfactory efficacy. Previously, we successfully non-invasively detected C4d, a specific marker for AMR diagnosis, in allografts using C4d-targeted microbubbles (MBC4d). In this study, we extended this approach by incorporating nitric oxide (NO), as high NO levels manifest immunosuppressive and anti-thrombotic effects. METHODS We designed novel MBC4d loaded with NO (NO-MBC4d). A rat model of AMR was established by pre-sensitization with skin transplantation. Contrast-enhanced ultrasound (CEUS) images were obtained and quantitatively analyzed following NO-MBC4d injection. Allograft survival and histologic features were analyzed to evaluate the therapeutic effect and underlying mechanism of NO-MBC4d toward AMR. RESULTS We successfully obtained CEUS images following NO-MBC4d injection and demonstrated that the ultrasound signal intensity of the myocardial area and clearance time of NO-MBC4d both increased with increased C4d grade, thereby realizing non-invasive diagnosis of AMR. Furthermore, allograft survival was significantly prolonged, and rejection was obviously attenuated following NO-MBC4d injection through significant suppression of thrombosis and reduction of inflammatory cell infiltrates. Overall, the therapeutic efficacy was significantly improved in the NO-MBC4d group compared with the control NO-MB group, demonstrating that precise treatment could significantly improve the therapeutic efficacy compared with that afforded by systemic applications. CONCLUSIONS This study presented a novel tool to provide simultaneous non-invasive diagnosis and precise treatment of AMR using NO-MBC4d CEUS imaging, which may be expected to provide a better option for recipients with AMR in clinic. |
| Databáze: | OpenAIRE |
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