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

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

American journal of physiology. Heart and circulatory physiology (2002-10-22)
Jürgen R Sindermann, Philip Babij, Joseph C Klink, Christiane Köbbert, Gabriele Plenz, Jan Ebbing, Li Fan, Keith L March
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Actin, α-Smooth Muscle, clone 1A4, ascites fluid
Sigma-Aldrich
Hybridization Solution, for Northern and Southern blotting, liquid (2x concentrate)