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

Jürgen R. Sindermann, Philip Babij, Joseph C. Klink, Christiane Köbbert, Gabriele Plenz, Jan Ebbing, Li Fan, Keith L. March

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)H2714-H2724
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
DOIs
StatePublished - Dec 1 2002

Keywords

  • Cell proliferation
  • Myosin heavy chain
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling'. Together they form a unique fingerprint.

  • Cite this