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Intracoronary Delivery of Adenovirus Encoding Adenylyl Cyclase VI Alters Murine Cardiac Fibroblast Function
Author(s) -
Cipta Stephanie Natalie,
Patel Hemal,
Lai N. Chin,
Yokoyama Utako,
Swaney James,
Gao Mei Hua,
Feramisco James,
Ross Robert,
Hammond H. Kirk,
Insel Paul,
Roth David
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.21.6.a1410-b
Intra‐coronary delivery of adenovirus encoding adenylyl cyclase VI (ACVI) increases LV function, by increased expression of ACVI in cardiac myocytes. In the current study we tested the hypothesis that this method of gene transfer would increase expression of ACVI in cardiac fibroblasts, and thereby alter fibroblast function. Adenovirus encoding EGFP (Ad.EGFP) or ACVI (Ad. ACVI) was delivered using indirect intracoronary injection in mice. One week after gene transfer, fibroblasts were isolated from hearts. Real‐time PCR of fibroblast DNA showed marked increase in adenovirus DNA (1800‐fold). In addition, ~80% of fibroblasts of mice that received Ad.EGFP were EGFP‐positive. Fibroblasts from Ad.AC VI treated hearts showed an increase in cAMP production relative to Ad.EGFP (8.4±0.2 vs. 4.6±0.7 pmol/well, n=3). Additional mice underwent Ad.EGFP or Adv. ACVI gene transfer followed by myocardial infarction (MI). Seven days after MI, cardiac fibroblasts were isolated from the non‐infarcted left ventricle (LV). Fibroblasts isolated from Ad. ACVI ‐treated mice showed blunted α‐smooth muscle actin expression in response to transforming growth factor‐β treatment compared to Ad.EGFP‐ treated mice. The results indicate that intracoronary delivery results in highly efficient transgene expression in murine cardiac fibroblasts. Furthermore, increased ACVI expression is associated with anti‐fibrotic activity of cardiac fibroblasts that may have favorable effects on LV remodeling.