© 2000 American Heart Association, Inc.
Editorial |
Hyperinsulinemia and Vascular Dysfunction: The Role of Nuclear Factor-
B, Yet Again
From the College of Physicians & Surgeons, Columbia University, New York, NY.
Correspondence to Dr Ann Marie Schmidt, College of Physicians & Surgeons, Columbia University, 630 W 168th St, P&S 17-501, New York, NY 10032. E-mail ams11@columbia.edu \ © 2000 American Heart Association, Inc.
Key Words: insulin • oxidant stress • Rho GTPases • nuclear factor-
B
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Introduction |
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Syndromes of type 2 diabetes and insulin resistance are accompanied by varying degrees of hyperinsulinemia. To date, a number of epidemiological studies have suggested that elevated levels of circulating insulin contribute independently to cardiovascular risk.1 2 It is not surprising, however, that some studies demonstrated no, or marginally increased, risk for cardiovascular complications,3 4 as it is clear that insulin is not the sole culprit. Other factors, such as hyperlipidemia and even intermittently elevated levels of blood glucose, are tightly linked to syndromes characterized by elevated levels of insulin. The key, therefore, to pinpointing the potentially adverse effects of insulin on the vessel wall concerns analysis of its effects on specific properties of vascular cells.
In this issue of Circulation Research,
Golovchenko et al5
have focused on the role of insulin in activation of the pleiotropic
transcription factor nuclear factor-B (NF-B). This is a logical
target, as evidence mounts to support a role for activation of NF-B
in the pathogenesis of
atherosclerosis,6 7
ischemia-reperfusion
injury,8 9
and
diabetes.10 11
For example, target genes of NF-B, such as tumor necrosis factor-
(TNF-) and vascular cell adhesion molecule-1, have long been
speculated to participate in the earliest stages of atherogenesis.
Indeed, RelA/p65, one of the components of NF-B, has been identified
within the nuclei of vascular smooth muscle cells (VSMCs) and
mononuclear phagocytes in human
atheromata.12 The
key question arises, therefore, what are the molecular triggers that
switch on NF-B in the vessel wall?
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Activation of NF-B: Role of AGEs
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In this context, a mixed
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