Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling.
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.
Sindermann
Jürgen R
JR
Krannert Institute of Cardiology and Indiana Center for Vascular Biology and Medicine, Indiana University Medical Center, Indianapolis 46202, USA. sinderm@uni-muenster.de
Babij
Philip
P
Klink
Joseph C
JC
Köbbert
Christiane
C
Plenz
Gabriele
G
Ebbing
Jan
J
Fan
Li
L
March
Keith L
KL
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
D000952:Antigens, Polyomavirus Transforming; D018809:Proliferating Cell Nuclear Antigen; D024745:Smooth Muscle Myosins