Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling

• Published in: American journal of physiology. Heart and circulatory physiology 2002-12, Vol.283 (6), p.H2714-H2724
• Main Authors: Sindermann, Jurgen R, Babij, Philip, Klink, Joseph C, Kobbert, Christiane, Plenz, Gabriele, Ebbing, Jan, Fan, Li, March, Keith L
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - genetics; Animals; Antigens, Polyomavirus Transforming - biosynthesis; Antigens, Polyomavirus Transforming - genetics; Arteries - cytology; Arteries - metabolism; Cell Count; Cell Division - genetics; Cell Division - physiology; Gene Expression - physiology; Mice; Mice, Inbred C3H; Mice, Transgenic; Models, Animal; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Proliferating Cell Nuclear Antigen - biosynthesis; Promoter Regions, Genetic; Rabbits; Simian virus 40 - genetics; Smooth Muscle Myosins - genetics; Stress, Mechanical; Vascular Patency
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00077.2002

1  Krannert Institute of Cardiology and Indiana Center for Vascular Biology and Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202; 2  Department of Cardiology and Angiology and 3  Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany; and 4  Wyeth Genetics Institute, Andover, Massachusetts 01810 To study the effects of enhanced smooth muscle cell (SMC) proliferation on arterial vessel geometry in the absence of vessel trauma, we developed a transgenic mouse model expressing SV40 large T antigen under control of the 2.3-kb smooth muscle-myosin heavy chain promoter. Transgenic mice studied at ages from 3 to 13 wk showed a 3.2-fold increase in arterial wall SMC density, with 28% of SMC exhibiting proliferative cell nuclear antigen staining, confirming enhanced SMC proliferation, which was accompanied by two- to threefold increases in arterial wall areas ( P