The Effects of Acarbose Treatment on Intimal Hyperplasia in a Rat Carotid Endarterectomy Model of Diet-Induced Insulin Resistance

Nyalala, John O.; Luo, Shaoke; Campbell, Doug; Brown, Aliza; Moursi, Mohammed M.

doi:10.1177/1538574410377019

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…[2] Upregulated ROS production is implicated in atherosclerosis and restenosis. [2, 31–33] Our studies suggest that HFHSD accelerates atherosclerotic lesions and increases intimal hyperplasia,[15–18] which might be in part via increased ROS production, irreversible SERCA oxidation, and induced inflammation.…”

Section: Discussionmentioning

confidence: 98%

“…[14], accelerates atherosclerotic lesions in minipigs and in LDL receptor deficient mice,[15–17] and increases intimal hyperplasia after rat carotid endarterectomy. [18] Compared to another commonly used obesity model induced by high fat diet without sucrose,[19, 20] HFHSD fed mice gain less weight and have less insulin resistance. [21] These two obese models both develop glucose intolerance, insulin resistance, cardiac hypertrophy and myocardial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells

Qin¹,

Hou²,

Weisbrod³

et al. 2014

Journal of Molecular and Cellular Cardiology

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Diet-induced obesity and metabolic syndrome are important contributors to cardiovascular diseases. The decreased nitric oxide (NO) bioactivity in endothelium and the impaired response of smooth muscle cell (SMC) to NO significantly contribute to vascular pathologies, including atherosclerosis and arterial restenosis after angioplasty. Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) is an important mediator of NO function in both endothelial cells and SMCs, and its irreversible oxidation impair its stimulation by NO. We used C57BL/6J mice fed a high fat, high sucrose diet (HFHSD) to study the role of SMC SERCA in diet-induced obesity and metabolic syndrome. We found that HFHSD upregulated Nox2 based NADPH oxidase, induced inflammation, increased irreversible SERCA oxidation, and suppressed the response of aortic SERCA to NO. Cultured aortic SMCs from mice fed HFHSD showed increased reactive oxygen species production, Nox2 upregulation, irreversible SERCA oxidation, inflammation, and a decreased ability of NO to inhibit SMC migration. Overexpression of wild type SERCA2b or downregulation of Nox2 restored NO-mediated inhibition of migration in SMCs isolated from HFHSD-fed mice. In addition, tumor necrosis factor alpha (TNFα) increased Nox2 which induced SERCA oxidation and inflammation. Taken together, Nox2 induced by HFHSD plays significant roles in controlling SMC responses to NO and TNFα-mediated inflammation, which may contribute to the development of cardiovascular diseases in diet-induced obesity and metabolic syndrome.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells

Qin¹,

Hou²,

Weisbrod³

et al. 2014

Journal of Molecular and Cellular Cardiology

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“…Treatment with metformin significantly improved these metabolic abnormalities. The observed effects of metformin are supported by the evidence that metformin decreases hepatic production of glucose and increases hepatic insulin sensitivity and glucose clearance [25,26]. …”

Section: Discussionmentioning

confidence: 99%

The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats

Lü

Meng

et al. 2013

Cardiovasc Diabetol

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BackgroundInsulin resistance is strongly associated with the development of type 2 diabetes and cardiovascular disease. However, the underlying mechanisms linking insulin resistance and the development of atherosclerosis have not been fully elucidated. Moreover, the protective effect of antihyperglycemic agent, metformin, is not fully understood. This study investigated the protective effects and underlying mechanisms of metformin in balloon-injury induced stenosis in insulin resistant rats.MethodsAfter 4 weeks high fructose diet, rats received balloon catheter injury on carotid arteries and were sacrificed at 1 and 4 weeks post injury. Biochemical, histological, and molecular changes were investigated.ResultsPlasma levels of glucose, insulin, total cholesterol, triglyceride, free fatty acids, and methylglyoxal were highly increased in fructose-induced insulin resistant rats and treatment with metformin significantly improved this metabolic profile. The neointimal formation of the carotid arteries was enhanced, and treatment with metformin markedly attenuated neointimal hyperplasia. A significant reduction in BrdU-positive cells in the neointima was observed in the metformin-treated group (P < 0.01). Insulin signaling pathways were inhibited in insulin resistant rats while treatment with metformin enhanced the expression of insulin signaling pathways. Increased expression of JNK and NFKB was suppressed following metformin treatment. Vasoreactivity was impaired while treatment with metformin attenuated phenylephrine-induced vasoconstriction and enhanced methacholine-induced vasorelaxation of the balloon injured carotid arteries in insulin resistant rats.ConclusionThe balloon-injury induced neointimal formation of the carotid arteries is enhanced by insulin resistance. Treatment with metformin significantly attenuates neointimal hyperplasia through inhibition of smooth muscle cell proliferation, migration, and inflammation as well as by improvement of the insulin signaling pathway.

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“…In many studies metformin has reduced both total cholesterol and LDL cholesterol levels [8486] , tri glyceride levels [84] and increased HDL levels [87,88] . Animal studies have shown that acarbose given to insulin resistant rats decreased carotid intimal hyperplasia and blood flow velocities [89] . Taken as a whole, the ability of metformin (and likely other insulin sensitizing agents) to elicit an over all reduction in the risk for CAD may be easier than the ability to produce consistent measureable improvements.…”

Section: Treatmentmentioning

confidence: 99%

Assessing and treating insulin resistance in women with polycystic ovarian syndrome

Traub¹

2011

WJD

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Polycystic ovarian syndrome (PCOS) is a highly pre valent hormonal and metabolic disorder among repro ductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for men strual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is under appreciated. Insulin resistance may be the first im portant marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery di sease.

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The Effects of Acarbose Treatment on Intimal Hyperplasia in a Rat Carotid Endarterectomy Model of Diet-Induced Insulin Resistance

Abstract: Glucose control by acarbose in rat carotid endarterectomy model of diet-induced insulin resistance resulted in attenuation of intimal hyperplasia.

Cited by 6 publications

References 38 publications

Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells

Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells

The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats

Assessing and treating insulin resistance in women with polycystic ovarian syndrome

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