Transplantation of cardiotrophin-1–expressing myoblasts to the left ventricular wall alleviates the transition from compensatory hypertrophy to congestive heart failure in Dahl salt-sensitive hypertensive rats
| Autor: | Ryuji Toh, Sonoko Hirayama, Mitsuhiro Yokoyama, Miki Kawai, Seinosuke Kawashima, Seimi Satomi-Kobayashi, Tomomi Ueyama, Tsuyoshi Sakoda |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Cardiotrophin 1 Cell Survival Cell Transplantation Heart Ventricles Myoblasts Skeletal Blood Pressure Muscle hypertrophy Diastole Internal medicine medicine Animals Autologous transplantation Ventricular remodeling Heart Failure Neurotransmitter Agents Rats Inbred Dahl Ventricular Remodeling business.industry Myocardium Gene Transfer Techniques Models Cardiovascular medicine.disease Myocardial Contraction Rats Up-Regulation Vasodilation Transplantation Disease Models Animal Endocrinology Echocardiography Heart failure Circulatory system Electrocardiography Ambulatory Cardiology Cytokines Hypertrophy Left Ventricular Endothelin receptor business Cardiology and Cardiovascular Medicine Biomarkers |
| Zdroj: | Journal of the American College of Cardiology. 43(12):2337-2347 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2004.02.048 |
| Popis: | Objectives We investigated whether autologous transplantation of skeletal myoblasts (MB) transferred with cardiotrophin-1 (CT-1) gene could retard the transition to heart failure (HF) in Dahl salt-sensitive (DS) hypertensive rats. Background Although MB is a therapeutic candidate for chronic HF, little is known about the efficiency of this strategy when applied in nonischemic HF. Cardiotrophin-1 has potent hypertrophic and survival effects on cardiac myocytes. We hypothesized that transplantation of CT-1–expressing myoblasts could provide cardioprotective effects against ventricular remodeling in DS hypertensive rats. Methods The DS rats were fed a high salt diet for 6 weeks and developed left ventricular (LV) hypertrophy at 11 weeks. At this stage, animals underwent MB to the myocardium with skeletal myoblasts transferred with CT-1 gene using retrovirus (transplantation of CT-1–expressing myoblasts [MB + CT], n = 31) or myoblasts alone (MB, n = 31). The sham group rats were injected with phosphate-buffered saline (n = 24). Results At 17 weeks, MB and MB + CT groups showed a significant alleviation of LV dilation and contractile dysfunction compared with the sham group. The degree of alleviation was significantly greater in the MB + CT group than the MB group (LV end-diastolic dimension: sham 7.06 ± 0.14 mm, MB 6.51 ± 0.16 mm, MB + CT 6.24 ± 0.07 mm; fractional shortening: sham 32.1 ± 1.4%, MB 38.5 ± 1.5%, MB + CT 43.2 ± 0.8%). Histological examination revealed that the myocyte size was 20% larger in the MB + CT group at 17 weeks than in the age-matched sham group. Upregulation of renin-angiotensin and endothelin systems during the transition to HF was attenuated by myoblast transplantation, and this effect was enhanced in the MB + CT group. Conclusions Transplantation of skeletal myoblasts combined with CT-1-gene transfer could be a useful therapeutic strategy for HF. |
| Databáze: | OpenAIRE |
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