Hyperhomocysteinemia increases intimal hyperplasia in a rat carotid endarterectomy model

Southern, Fredrick N.; Cruz, Nestor Dela; Fink, Louis M.; Cooney, Craig A.; Barone, Gary W.; Eidt, John F.; Moursi, Mohammed M.

doi:10.1016/s0741-5214(98)70069-2

Cited by 54 publications

(51 citation statements)

References 28 publications

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“…Therefore, an elevated serum Hcy level might be partially responsible for the impaired ocular blood flow in HTCs. Southern et al (1998) reported that a Hcysupplemented diet produced elevated serum Hcy levels and subsequently increased intimal hyperplasia, with a resultant increase in luminal stenosis in a rat model. In another rat model, smoking significantly increased serum Hcy levels and luminal stenosis, and folic acid supplementation attenuated this effect (Davis et al 2004); however, none of the cases in our study was taking folic acid or smoking cigarettes.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of the general population have suggested associations between mild elevations of plasma homocysteine (Hcy) levels and coronary, cerebral, and peripheral atherosclerosis such as orbital occlusive disease (Taylor et al 1991;Wilcken 1998;Southern et al 1998;Uysal et al 2005). Increased intima media thickness (IMT) is generally considered an early marker of atherosclerosis (Erdogmus et al 2006) and causes a decrease in blood flow velocity.…”

Section: Ultrasonic Examinationmentioning

confidence: 99%

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High Serum Homocysteine Levels Correlate with a Decrease in the Blood Flow Velocity of the Ophthalmic Artery in Highway Toll Collectors

Memişoğulları

Yüksel

Coşkun

et al. 2007

Tohoku J. Exp. Med.

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Highway workers, such as policemen, automotive service companies, and toll collectors, are placed at risk of the accelerated atherosclerotic process, since recent studies have suggested that exposure to exhaust particles and ambient air pollution increases carotid intima-media thickness and reduces ocular blood flow velocity. Therefore, we assessed the relationship between serum homocysteine, a potential parameter for atherosclerosis, and the ocular blood flow velocity and the resistivity index in highway toll collectors. The peak systolic and end diastolic flow velocities and the resistivity index were measured in 22 toll collectors and 24 control subjects by color Doppler ultrasonography. The resistivity index, which is an indirect measure of the atherosclerotic process, was calculated: resistivity index = (peak systolic velocity -end diastolic velocity)/peak systolic velocity. Serum homocysteine levels were determined by fluorometric high-performance liquid chromatography. In the highway toll collectors, the serum homocysteine level (14.4 ± 4.8 μ mol/l; p < 0.005) and the resistivity index of the ophthalmic artery (0.741 ± 0.015; p < 0.05) were higher and the ophthalmic blood flow velocity (33.0 ± 3.0 cm/s; p < 0.001) was lower than those in the controls (10.6 ± 3.1 μ mol/l; 0.728 ± 0.023; 36.8 ± 2.2 cm/s; respectively). There were significant correlations between the serum homocysteine level and ophthalmic artery resistivity index in both highway toll collectors ( p < 0.001) and controls ( p < 0.005). Exposure to exhaust particles might increase the serum homocysteine level, which in turn could lead to the decreased ocular blood flow and the increased resistivity index.homocysteine; ocular blood flow; highway toll collectors; color Doppler ultrasonography

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Section: Discussionmentioning

confidence: 99%

Section: Ultrasonic Examinationmentioning

confidence: 99%

High Serum Homocysteine Levels Correlate with a Decrease in the Blood Flow Velocity of the Ophthalmic Artery in Highway Toll Collectors

Memişoğulları

Yüksel

Coşkun

et al. 2007

Tohoku J. Exp. Med.

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“…Dietinduced hyperhomocysteinemia is associated with vascular dysfunction in the monkey, probably due to the inhibition of nitric oxide (NO) synthesis, 1 linked with vascular structural damage in the minipig because of elastic lamina fragmentation, 2 correlated with increased postinjury intimal hyperplasia, 3 and impaired endothelial function and leukocyte-endothelium interaction in the rat. 4 A genetic hyperhomocysteinemia model with the gene deletion of cystathionine ␤-synthase (CBS), which catalyzes Hcy to cystathionine, has been used in studies of Hcy pathology.…”

Section: Introductionmentioning

confidence: 99%

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

Wang

Jiang

Yang

et al. 2003

Blood

178

155

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Although hyperhomocysteinemia is an independent risk factor for cardiovascular disease, a direct role for homocysteine (Hcy) in this disease remains to be shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in animal models, the effects of Hcy on atherogenesis in the absence of dietary perturbations is not known. We have generated double knock-out mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine ␤-synthase (CBS), which converts Hcy to cystathionine. ApoE ؊/؊ /CBS ؊/؊ mice developed aortic lesions even in the absence of dietary manipulation; lesion area and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with animal age and plasma Hcy levels. Plasma total cholesterol was significantly increased, whereas high density lipoprotein (HDL) cholesterol and TG concentrations of apoE ؊/؊ /CBS ؊/؊ mice were decreased. Cholesterol esterification and activities of enzymes catalyzing CE or TG formation in the vessel wall and in peritoneal macrophages were not changed by hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native low density lipoprotein (LDL), by mouse peritoneal macrophages was higher in the presence of hyperhomocysteinemia. These results suggest that isolated hyperhomocysteinemia is atherogenic and alters hepatic and macrophage lipoprotein metabolism, in part, by enhancing uptake of modified LDL. (Blood. 2003;101: 3901-3907)

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“…Morphometric analyses were performed as described previously by Southern et al [19]. In brief, after dehydration with increasing alcohol concentrations, aliquots were embedded in paraffin, and 5-lm sections from two locations 100 lm apart were prepared.…”

Section: Histomorphometrymentioning

confidence: 99%

The Cardiac Effects of Prolonged Vitamin B12 and Folate Deficiency in Rats

et al. 2009

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In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The impact of these vitamins on cardiac function and morphology has scarcely been investigated. The aim of this study was to conduct an analysis of the cardiac effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for 12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet. Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S-adenosyl-methionine (SAM), and brain natriuretic peptide (BNP) were measured. Moreover, echocardiographic and histomorphometric analyses were performed. VitDef animals developed a significant HHCY (Co vs VitDef: 6.8 +/- 2.7 vs 61.1 +/- 12.8 micromol/l, P < 0.001). Fractional shortening, left ventricular dimension at end-diastole and end-systole, posterior wall thickness, perivascular collagen, mast cell number, and BNP tissue levels were comparable in VitDef and Co animals. Interstitial collagen (Co vs VitDef: 6.8 +/- 3.0 vs 4.5 +/- 2.1%, P < 0.05), plasma BNP (Co vs VitDef: 180 +/- 80 vs 70 +/- 60 ng/l, P < 0.05), and tissue HCY (Co vs VitDef: 0.13 +/- 0.07 vs 0.07 +/- 0.04 micromol/g protein, P < 0.05) were lower in VitDef animals. Folate and vitamin B12 deficiency do not affect cardiac function and morphology.

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Hyperhomocysteinemia increases intimal hyperplasia in a rat carotid endarterectomy model

Cited by 54 publications

References 28 publications

High Serum Homocysteine Levels Correlate with a Decrease in the Blood Flow Velocity of the Ophthalmic Artery in Highway Toll Collectors

High Serum Homocysteine Levels Correlate with a Decrease in the Blood Flow Velocity of the Ophthalmic Artery in Highway Toll Collectors

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

The Cardiac Effects of Prolonged Vitamin B12 and Folate Deficiency in Rats

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