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- Title
Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine.
- Authors
Darla L. Tharp; Isabelle Masseau; Jan Ivey; Venkataseshu K. Ganjam; Douglas K. Bowles
- Abstract
Aims Previous studies from our laboratory have demonstrated that testosterone increases coronary smooth muscle protein kinase C delta (PKCδ) both in vivo and in vitro and inhibits coronary smooth muscle proliferation by inducing G0/G1 cell cycle arrest in a PKCδ-dependent manner. The purpose of the present study was to determine whether endogenous testosterone limits coronary neointima (NI) formation in a porcine model of post-angioplasty restenosis. Methods and results Sexually mature, male Yucatan miniature swine were either left intact (IM), castrated (CM), or castrated with testosterone replacement (CMT; Androgel, 10 mg/day). Angioplasty was performed in both the left anterior descending and left circumflex coronary arteries with balloon catheter overinflation to induce either moderate (1.25–1.3x diameter; 3 × 30 s) or severe (1.4x diameter; 3 × 30 s) injury, and animals were allowed to recover for either 10 or 28 days. Injured coronary sections were dissected, fixed, stained (Verheoff-Van Gieson, Ki67, PKCδ, p27), and analysed. Vessels without internal elastic laminal rupture were excluded. Following moderate injury, intimal area, intima-to-media ratio (I/M), and I/M normalized to rupture index (RI) were increased in CM compared with IM and CMT. RI, medial area, and intimal/medial thickness (IMT) were not different between groups. NI formation was inversely related to serum testosterone concentration. Conversely, following severe injury, there were no significant differences between the groups. Testosterone inhibited proliferation and stimulated PKCδ and p27kip1 expression during NI formation (10 days post-injury). Conclusion These findings demonstrate that endogenous testosterone limits coronary NI formation in male swine and provides support for a protective role for testosterone in coronary vasculoproliferative diseases, such as restenosis and atherosclerosis.
- Publication
Cardiovascular Research, 2009, Vol 82, Issue 1, p152
- ISSN
0008-6363
- Publication type
Academic Journal
- DOI
10.1093/cvr/cvp038