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Title of article :
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 Original Research Article
Author/Authors :
Ryuji Toh، نويسنده , , Seinosuke Kawashima، نويسنده , , Miki Kawai، نويسنده , , Tsuyoshi Sakoda، نويسنده , , Tomomi Ueyama، نويسنده , , Seimi Satomi-Kobayashi، نويسنده , , Sonoko Hirayama، نويسنده , , Mitsuhiro Yokoyama، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
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Abstract :
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.
Keywords :
heart failure , angiotensin II , endothelin-1 , Public beliefs , ET-1 , Hf , PWT , DS , LV , posterior wall thickness , percent fractional shortening , left ventricle or left ventricular , Ang II , CT-1 , cardiotrophin-1 , Dahl salt-sensitive , EDD , end-diastolic dimension , MB , transplantation of skeletal myoblasts alone , MB + CT , transplantation of cardiotrophin-1–expressing myoblasts
Journal title :
JACC (Journal of the American College of Cardiology)
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