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Adrenomedullin gene transfer induces neointimal apoptosis and inhibits neointimal hyperplasia in injured rat artery
Author(s) -
RaumaPinola Tanja,
Pääkkö Paavo,
Ilves Mika,
Serpi Raisa,
Romppanen Hannu,
Vuolteenaho Olli,
Ruskoaho Heikki,
Hautala Timo
Publication year - 2006
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.865
Subject(s) - neointimal hyperplasia , neointima , vascular smooth muscle , myofibroblast , adrenomedullin , apoptosis , paracrine signalling , medicine , cancer research , endocrinology , chemistry , restenosis , smooth muscle , receptor , biochemistry , stent , fibrosis
Arterial wall injury leads to inflammatory reaction and release of growth factors that may mediate intimal regrowth. It is hypothesized that the neointimal cells may originate from adventitial myofibroblasts, medial smooth muscle cells, or differentiated bone marrow derived cells. Adrenomedullin (AM), an auto/paracrine cardiovascular peptide that is secreted from fibroblasts, endothelial cells, and vascular smooth muscle cells, may have a regulatory role in the intimal regeneration. In order to investigate the role of AM in neointimal growth, stimulation of stem cell migration, and apoptosis, we overexpressed AM with recombinant adenovirus in a rat arterial injury model. The intimae were significantly thinner in the arteries treated with AM adenovirus compared to the control group. Intima/media ratios were 0.48 ± 0.18 and 1.01 ± 0.20 ( P < 0.05) in the AM group and the control group, respectively. In addition, a significantly higher apoptotic index of neointimal cells was seen in the AM gene transfer group compared to the control (2.78 ± 0.5 vs. 0.57 ± 0.20, P < 0.01). The neointimal cells stained positive for α‐smooth muscle actin and negative for desmin suggesting possible myofibroblast origin. Very few c‐Kit+ or MDR1+ cells were detected 2 weeks after the injury. We conclude that AM overexpression inhibits neointimal growth. The inhibition is associated with enhanced apoptosis of the neointimal cells which may be of myofibroblast origin. Copyright © 2006 John Wiley & Sons, Ltd.