Abstract
The aim of this work was to elucidate the effect of cyclic nucleotide signaling on the growth of vascular smooth muscle cells (VSMCs). In particular, the role of cGKI in VSMC growth was analysed in primary and subcultured VSMCs derived from wild-type and cGKI-deficient mice. In primary VSMCs, activation of cGMP/cGKI signaling led to a strong increase in growth. In contrast, in repeatedly passaged VSMCs derived from mouse, rat and human, cGMP/cGKI had either no effect on growth or had a weak growth suppressing effect. Thus, cGKI signaling differs in primary vs. subcultured VSMCs. The further analysis of proliferation, apoptosis, cytoskeletal dynamics, and various signaling pathways indicated that an increase in integrin-mediated cell adhesion is the major mechanism for cGKI-mediated growth in primary VSMCs. Thereby, cGMP/cGKI signaling in primary VSMCs might inhibit anoikis, the programmed cell death induced by the loss of cell/matrix interactions.
Highlights
Pascal Weinmeister*1, Robert Lukowski1, Stefan Linder2, Wolfgang Erl2, Richard Brandl3, Susanne Feil1, Franz Hofmann1 and Robert Feil1
Recent in vivo studies with transgenic mice indicated that cGMP/cGMP-dependent protein kinase type I (cGKI) signaling in vascular smooth muscle cells (VSMCs) promotes vasculo-proliferative processes
All tested agonists stimulated the growth of primary VSMCs via activation of cGKI, whereas the tested "cGK inhibitors" failed to inhibit cGKI activity and cell growth. 8-Br-cAMP, an activator of the cAMP-dependent protein kinase, inhibited the growth of both wild-type and cGKI-deficient cells
Summary
Pascal Weinmeister*1, Robert Lukowski1, Stefan Linder2, Wolfgang Erl2, Richard Brandl3, Susanne Feil1, Franz Hofmann1 and Robert Feil1. Regulation of vascular smooth muscle growth by cyclic nucleotides and cGMP-dependent protein kinase Address: 1Institut für Pharmakologie und Toxikologie, TU München, Germany, 2Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, LMU München, Germany and 3Krankenhaus München Schwabing, Gefäβchirurgie, Germany
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