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Lenti‐Angiotensin‐(1–7) transduction of Islet+ cardiac progenitor cells improves the reparative capacity in Doxorubicin induced Cardiomyopathy
Author(s) -
Bruce Erin,
Qi Yanfei,
Horowitz Alana,
Raizada Mohan K.,
Katovich Michael J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1184.7
Subject(s) - doxorubicin , medicine , cardiomyopathy , heart failure , progenitor cell , myocardial infarction , cardiology , ischemic cardiomyopathy , angiotensin ii , pharmacology , chemotherapy , ejection fraction , stem cell , biology , blood pressure , microbiology and biotechnology
Doxorubicin (DOX), a highly effective antineoplastic agent, can have devastating effects on the heart. Recent studies indicate that cardiac progenitor cell (CPC) loss plays a major role in the pathophysiology of DOX‐induced cardiomyopathy. We have recently demonstrated the potential for Angiotensin‐(1–7) (Ang‐(1–7)) to improve the beneficial effects of CPCs when given as therapy in a model of myocardial infarction. We hypothesize that giving CPCs transduced with lenti‐Ang‐(1–7) will further improve the regenerative capabilities of CPC therapy in DOX‐induced cardiomyopathy. Male SD rats were injected via tail vein with 2.5mg/kg/week DOX for 5 weeks, reaching a cumulative dose of 12.5mg/kg. 4 × 10^8 Islet+ CPCs, or lenti‐Ang‐(1–7) CPCs, were injected via jugular vein 3 days post Dox injection at weeks 3 and 5. Hemodynamic parameters were measured 2 weeks later. DOX significantly reduced dP/dtmax (3769 ± 322 vs 6880 ± 345 for control, mmHg/sec) and ventricular mass (VM, 1.75 ± 0.09 vs 3.07 ± 0.2 for control, (g/cm)). In comparison to DOX, CPCs alone restored dP/dtmax by 7.5% and increased VM by 5.3%. Ang‐(1–7) expressing CPCs further improved dP/dtmax by 13.8%, and increased VM by 8.3%. Ang‐(1–7) transduced CPCs seems to further improve the reparative capacity of CPC therapy and may prove to be a significantly beneficial therapy in preventing DOX‐induced cardiomyopathy.