Gary L. Baumbach, Sean P. Didion and Frank M. Faraci
Hypertrophy of Cerebral Arterioles in Mice Deficient in Expression of the Gene for CuZn
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that favors O2
cantly reduced in CuZnSOD?/?mice.28Furthermore, if H2O2
is an important stimulus of cellular growth in response to
oxidative stress, we would anticipate that overexpression of
CuZnSOD would increase levels of H2O2 and accelerate
cellular growth. At least with fibroblasts, however, overex-
pression of CuZnSOD suppresses growth and induces fea-
tures of cell senescence, despite elevated levels of H2O2.29
Thus, our findings in this intact system support the concept
that ROS influence vascular growth, but provide new evi-
dence to suggest O2
hypertrophy in vivo.
–. This expectation is borne out by the finding
–levels are increased and levels of H2O2are signifi-
–may be a key mediator of vascular
We found in this study that (1) cerebral arterioles in both
CuZnSOD?/?and CuZnSOD?/?mice undergo hypertrophy
and (2) the degree of hypertrophy is greater in CuZnSOD?/?
mice than previously observed in homozygous eNOS-
deficient mice.7Based on these findings we conclude that
interactions of O2
degree of cerebral arteriolar hypertrophy found in CuZnSOD?/?
mice. Our study provides genetic support for the concept that
ROS influence vascular growth and CuZnSOD may play an
important role in the regulation of vascular growth.
–with NO cannot account entirely for the
We thank Tom Gerhold, Shams Ghoneim and Cynthia Lynch for
technical assistance, and Norma Sinclair and the University of Iowa
Transgenic Facility for genotyping services.
Sources of Funding
This work was supported by National Institutes of Health Grants
HL-22149, NS-62461, HL-38901 and HL-62984, and an American
Heart Association grant (0230327N).
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Baumbach et alVascular Structure in CuZnSOD-Deficient Mice
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