title: Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling.
abstract: 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 < 0.05). Remarkably, despite increased vessel wall mass, the lumen area was not compromised, but rather was increased. A tightly conserved linear relationship was found between arterial circumference and wall thickness with slopes of 0.036 for both transgenics (r = 0.93, P < 0.01) and controls (r = 0.77, P < 0.01), suggesting the hypothesis that the conservation of wall stress functions as a primary determinant of adaptive arterial remodeling. This establishes a new model of adaptive vessel remodeling occurring in response to a proliferative input in the absence of mechanical injury or primary flow perturbation.
authors.affiliation: Krannert Institute of Cardiology and Indiana Center for Vascular Biology and Medicine, Indiana University Medical Center, Indianapolis 46202, USA. sinderm@uni-muenster.de
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Sindermann
authors.forename: Philip
authors.initials: P
authors.lastname: Babij
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Klink
authors.forename: Christiane
authors.initials: C
authors.lastname: Köbbert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Plenz
authors.forename: Jan
authors.initials: J
authors.lastname: Ebbing
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000235:genetics; D001158:Arteries / Q000166:cytology / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D011817:Rabbits; D013539:Simian virus 40 / Q000235:genetics*; D024745:Smooth Muscle Myosins / Q000235:genetics; D013314:Stress, Mechanical; D014654:Vascular Patency
chemical_list: D000952:Antigens, Polyomavirus Transforming; D018809:Proliferating Cell Nuclear Antigen; D024745:Smooth Muscle Myosins