Treatment of Acute Myocardial Infarction by Hepatocyte Growth Factor Gene Transfer
| Autor: | Koji Ohmori, Masakazu Kohno, Sachiko Fuke, Tsunetatsu Namba, Kaori Shinomiya, Isao Kondo, Hiroto Takeuchi, Takahisa Noma, Akira Oshita |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Pathology business.industry Angiogenesis Genetic enhancement Genetic transfer Infarction medicine.disease Internal medicine Cardiology Systemic administration Medicine Hepatocyte growth factor Myocardial infarction business Ventricular remodeling Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of the American College of Cardiology. 44(3):644-653 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2004.04.042 |
| Popis: | Objectives We examined whether ultrasonic microbubble destruction (US/MB) enables therapeutic myocardial gene transfer of hepatocyte growth factor (HGF) for acute myocardial infarction (MI). Background Hepatocyte growth factor gene transfer provides cardioprotective effects in MI, which requires direct intramyocardial injection or special vectors. Although US/MB was used in myocardial gene transfer, its feasibility in transfer of a therapeutic gene with non-viral vector remains unknown. Methods In a rat model of acute MI, naked plasmid (pVax1) encoding human HGF (1,500 μg) was infused into the left ventricular (LV) chamber during US/MB (HGF-US/MB) or insonation only (HGF-US) or alone (HGF-alone), while control MI rats received empty pVax1 during US/MB (pVax1-US/MB). For US/MB, transthoracic intermittent insonation with a diagnostic transducer (1.3 MHz) was performed for 2 min at a peak negative pressure of −2,160 kPa during intravenous 20% Optison. Results Baseline risk area was comparable among the groups. Immunohistology seven days after treatment revealed significant myocardial expression of HGF protein only in HGF-US/MB. At three weeks, LV weight in HGF-US/MB (0.89 ± 0.03 g) was significantly lower than those in HGF-alone (1.09 ± 0.08 g), HGF-US (1.04 ± 0.07 g), and pVax1-US/MB (1.04 ± 0.05 g). Moreover, scar size was significantly smaller (16 ± 6% vs. 39 ± 5%, 41 ± 6%, and 40 ± 4% of total myocardial circumferential length, respectively), while capillary density (49 ± 8 vs. 34 ± 5, 37 ± 6, and 36 ± 4 capillaries/high-power field, respectively) and arterial density (37 ± 7 vs. 15 ± 9, 18 ± 4, and 14 ± 11 arterioles/high-power field, respectively) in the risk area were higher in HGF-US/MB than the other groups. Conclusions Ultrasound-mediated microbubble destruction may enable myocardial HGF gene transfer with systemic administration of naked plasmid, which enhances angiogenesis, limits infarction size, and prevents LV remodeling after MI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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