Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Leitges, M; Mayr, M; Braun, U; Mayr, U; Li, C; Pfister, G; Ghaffari-Tabrizi, N; Baier, G; Hu, Y; Xu, Q.
Exacerbated vein graft arteriosclerosis in protein kinase Cdelta-null mice.
J Clin Invest. 2001; 108(10):1505-1512
Doi: 10.1172/JCI12902
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Ghaffari Tabrizi-Wizsy Nassim
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Smooth muscle cell (SMC) accumulation is a key event in the development of atherosclerosis, including vein bypass graft arteriosclerosis. Because members of the protein kinase C (PKC) family signal cells to undergo proliferation, differentiation, or apoptosis, we generated PKCdelta knockout mice and performed vein bypass grafts on these animals. PKCdelta(-/-) mice developed normally and were fertile. Vein segments from PKCdelta(-/-) mice isografted to carotid arteries of recipient mice of either genotype led to a more severe arteriosclerosis than was seen with PKCdelta(+/+) vein grafts. Arteriosclerotic lesions in PKCdelta(-/-) mice showed a significantly higher number of SMCs than were found in wild-type animals; this was correlated with decreased SMC death in lesions of PKCdelta(-/-) mice. SMCs derived from PKCdelta(-/-) aortae were resistant to cell death induced by any of several stimuli, but they were similar to wild-type SMCs with respect to mitogen-stimulated cell proliferation in vitro. Furthermore, pro-apoptotic treatments led to diminished caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and cytochrome c release in PKCdelta(-/-) relative to wild-type SMCs, suggesting that their apoptotic resistance involves the loss of free radical generation and mitochondrial dysfunction in response to stress stimuli. Our data indicate that PKCdelta maintains SMC homeostasis and that its function in the vessel wall per se is crucial in the development of vein graft arteriosclerosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Arteriosclerosis - enzymology
- Blood Vessel Prosthesis - enzymology
- Isoenzymes - genetics
- Mice - genetics
- Mice, Knockout - genetics
- Protein Kinase C - genetics
- Protein Kinase C-delta - genetics
- Protein Transport - genetics
- Veins - pathology