Biocompatible, Purified VEGF-A mRNA Improves Cardiac Function after Intracardiac Injection 1 Week Post-myocardial Infarction in Swine
| Autor: | Kenneth R. Chien, Susan Lin, Patrick C.H. Hsieh, Karin Jennbacken, Muhammad Waqas Sadiq, Francine Gregoire, Yu-Ping Wang, Christopher Y.T. Yen, Jonathan Clarke, Leif Carlsson, Gunilla Linhardt, Qing-Dong Wang, Regina Fritsche-Danielson, Li-Ming Gan, Edvin Johansson, Sofia Martinsson, Martin Billger, Ann-Charlotte Egnell, Nevin Witman, Barry Ticho, Tamsin Albery, Chien-Hsi Chen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inotrope Cardiac function curve medicine.medical_specialty lcsh:QH426-470 Intracardiac injection 03 medical and health sciences Internal medicine Genetics medicine Myocardial infarction lcsh:QH573-671 Molecular Biology Ejection fraction lcsh:Cytology business.industry Cardiac muscle medicine.disease lcsh:Genetics 030104 developmental biology medicine.anatomical_structure Heart failure cardiovascular system Cardiology Molecular Medicine Myocardial fibrosis business |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 9, Iss, Pp 330-346 (2018) |
| ISSN: | 2329-0501 |
| Popis: | mRNA can direct dose-dependent protein expression in cardiac muscle without genome integration, but to date has not been shown to improve cardiac function in a safe, clinically applicable way. Herein, we report that a purified and optimized mRNA in a biocompatible citrate-saline formulation is tissue specific, long acting, and does not stimulate an immune response. In small- and large-animal, permanent occlusion myocardial infarction models, VEGF-A 165 mRNA improves systolic ventricular function and limits myocardial damage. Following a single administration a week post-infarction in mini pigs, left ventricular ejection fraction, inotropy, and ventricular compliance improved, border zone arteriolar and capillary density increased, and myocardial fibrosis decreased at 2 months post-treatment. Purified VEGF-A mRNA establishes the feasibility of improving cardiac function in the sub-acute therapeutic window and may represent a new class of therapies for ischemic injury. Keywords: modRNA, mRNA, mRNA, VEGF, heart failure |
| Databáze: | OpenAIRE |
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