Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

Liao, Feng; Andalibi, Ali; Qiao, Jian-Hua; Allayee, Hooman; Fogelman, Alan M.; Lusis, Aldons J.

doi:10.1172/jci117409

Cited by 223 publications

(137 citation statements)

References 46 publications

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“…Others have shown increased measures of alternative oxidative stress markers, such as gene expressions of heme oxygenase-1, as well as activation of the oxidant stresssensitive transcription factor nuclear factor-B. 52,53 Clearly, this combination of oxidative and glycemic stress and sex hormones is very complex. Much work needs to be performed to elucidate mechanisms involved in the vascular response to these conditions.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

Walsh

Busch

Mullick

et al. 1999

ATVB

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Abstract-Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P 4 (200 mg progesterone), low estradiol and P 4 , placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiolϩP 4 ) exhibited a 50% reduction in glycoxidative damage compared with P 4 , placebo, and control vessels (PϽ0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (PϽ0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

Walsh

Busch

Mullick

et al. 1999

ATVB

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“…Thus the genes implicated in atherosclerosis susceptibility by this diet-induced model may reflect more about their relationship to an inflammatory diet than factors which may be more relevant to human disease. In fact, when the C57BL/6 ϫ C3H RI strain set was examined, there was concordance for atherosclerosis susceptibility and induction of these inflammatory markers [32].…”

Section: Diet-induced Atherosclerosismentioning

confidence: 93%

The emergence of mouse models of atherosclerosis and their relevance to clinical research

Smith

Breslow

1997

Journal of Internal Medicine

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Due to the ability to introduce or mutate genes, the mouse has become the most common experimental animal model for atherosclerosis research. Wildtype mice on a chow diet do not get atherosclerosis. Three ways to induce atherosclerosis in mice are discussed: diet-induced, apoE deficiency-induced, and LDL receptor-deficiency induced. The atherosclerotic lesions in apoE-deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. These mouse models of atherosclerosis are being used to identify genes which modify atherosclerosis susceptibility and in the development of antiatherogenic therapies.

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“…12,[22][23][24] Subsequent studies indicated a more complex picture. [25][26][27][28][29] As discussed later, the HDL component of the Ath1 phenotype proved to be caused by polymorphisms of apoA-II.…”

Section: Mapping Genes For Atherosclerosis In Micementioning

confidence: 99%

“…Genetic studies in mice have also revealed information about pathways that contribute to genetic susceptibility to atherosclerosis, particularly in relation to lipid oxidation 27 and inflammation. 29,39 It is noteworthy that most of the loci for atherosclerosis identified in mice do not influence plasma lipid levels, blood pressure, or other systemic risk factors (see references in Table 1).…”

Section: Mapping Genes For Atherosclerosis In Micementioning

confidence: 99%

Using Mice to Dissect Genetic Factors in Atherosclerosis

Allayee¹,

Ghazalpour²,

Lusis³

2003

ATVB

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Abstract-The genes that contribute to common, complex forms of atherosclerosis remain largely unknown. Genetic studies in humans have, for the most part, focused on identifying genes that predispose to the traditional risk factors, such as lipid levels and blood pressure, but apart from rare, single-gene disorders, there have been few successes to date. The use of mice to dissect the complex genetic etiology of atherosclerosis offers a viable alternative to human studies, because experimental parameters, such as environment, breeding scheme, and detailed phenotyping, can be controlled. Herein we review how mouse genetics can lead to the identification of genes, some of which would otherwise not have been considered as candidates for atherosclerosis, and provide an overview of the prospects for successful gene discovery in the future.

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Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

Cited by 223 publications

References 46 publications

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

The emergence of mouse models of atherosclerosis and their relevance to clinical research

Using Mice to Dissect Genetic Factors in Atherosclerosis

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