Lowering Homocysteine Decreases Levels and Expression of VEGF165 and Endostatin

Atta, Hussein M.; El-Rehani, Mahmoud A.; Raheim, Salama Abdel; Galal, Abdel Moneim F.

doi:10.1016/j.jss.2007.04.038

Cited by 10 publications

(7 citation statements)

References 69 publications

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“…Interestingly, our result suggested that Hcy had suppressive function on those signaling factors in a dose-dependent manner ( Figure 4 ). Our finding about Hcy and VEGF signaling pathway was supported by other researchers [ 15 , 50 ]. The connection between Hcy and Ang was first time reported in the field by us, which sheds more light on the mechanism of Hcy-mediated angiogenesis regulation.…”

Section: Discussionsupporting

confidence: 90%

Homocysteine inhibits angiogenesis through cytoskeleton remodeling

et al. 2017

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Homocysteine (Hcy) is an intermediate non-diet amino acid connecting methionine and folate cycles. Elevated total Hcy level in blood, denoted as hyperhomocysteinemia, has emerged as a prevalent and strong risk factor for multiple diseases including atherosclerotic vascular disease in coronary, cerebral, and peripheral vessels. Its detrimental effect on vascular system implies the potential application as an inhibitor of angiogenesis. However, the detailed mechanism is unveiled. Inhibitory effect of Hcy was assessed on vascular endothelial growth factor (VEGF) induced cell proliferation and migration with endothelial cell (EC) culture system. Its effect on angiogenesis was further examined in vitro and in vivo. After Hcy treatment, key angiogenic factors were measured by RT-qPCR. Cellular skeletal structure was also evaluated by actin stress fiber staining. VEGF-induced human umbilical vein EC (HUVEC) proliferation and migration were dramatically down-regulated by Hcy in a dose-responsive manner. Hcy treatment significantly inhibited the VEGF-induced angiogenesis in vitro by tube formation assay and chick chorioallantoic membrane (CAM) vessel formation in vivo. Key angiogenic factors like VEGFR1/2 and angiopoietin (Ang)1/2 were substantially reduced by Hcy in HUVEC- and VEGF-induced actin stress fiber cytoskeletal structure was abolished. We demonstrated that Hcy could inhibit angiogenesis by targetting key angiogenic factor and disruption of actin cytoskeleton which is crucial for cell migration.

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Section: Discussionsupporting

confidence: 90%

Homocysteine inhibits angiogenesis through cytoskeleton remodeling

et al. 2017

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“…67 Shastry et al 68 have reported that Hcy inhibits angiogenesis, partly by decreasing VEGF, as shown in an experiment using mouse brain microvascular endothelial cells. Furthermore, Atta et al 69 reported that lowering Hcy levels with vitamin B and folic acid results in a substantial reduction of VEGF plasma levels in patients with peripheral arterial disease or diabetes mellitus. Thus, it is possible that VEGF genotypes are associated with circulating tHcy levels.…”

Section: Discussionmentioning

confidence: 99%

Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

Hong

Kim

et al. 2011

Stroke

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Background and Purpose-Vascular endothelial growth factor (VEGF) plays a role in atherosclerosis-related diseases such as cerebrovascular or cardiovascular diseases. However, the effect of VEGF -2578CϾA, -1154GϾA, -634GϾC, and 936CϾT polymorphisms on the susceptibility to stroke and silent brain infarction has not been reported. Methods-Using polymerase chain reaction-amplified DNA, VEGF polymorphisms were analyzed in 615 patients with ischemic stroke, 376 patients with silent brain infarction, and 494 control subjects. Results-The AA and CCϩCA (C allele bearing) genotype frequencies of the -2578CϾA polymorphism and the CTϩTT (T allele-bearing) genotype frequency of the 936CϾT polymorphism were significantly different between the stroke and control groups (false discovery rate-adjusted probability values of 0.016, 0.044, and 0.044, respectively). When stratified by the size of the occluded vessel, the VEGF polymorphisms were associated with patients with multiple small-artery occlusions. Several haplotypes of the VEGF polymorphisms were significantly different between the control and stroke groups. With respect to silent brain infarction, the difference in the frequency of the -634GϾC polymorphism between the GCϩCC (C allele-bearing) genotype and the controls was marginally significant (false discovery rate-adjusted probability value of 0.056). On the other hand, the -634GϾC and 936CϾT polymorphisms were associated with plasma homocysteine levels of patients with multiple or single small-artery occlusions, respectively. Conclusions-This study suggests that VEGF polymorphisms and haplotypes are possible genetic determinants for the risk of ischemic stroke, particularly in patients with multiple small-artery occlusions. However, VEGF polymorphisms had only a weak association with plasma homocysteine levels in the Korean population. (Stroke. 2011;42:2393-2402.)

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“…Previous studies found increased homocysteine associated with diabetic retinopathy [7, 8]. The homocysteine affects vascular endothelial growth factor in the retina [9, 10], which is also associated with the regulation of angiogenesis [11]. Reducing homocysteine is one such approach that addresses another driver of DR, without impairing anti-VEGF and laser therapies.…”

Section: Introductionmentioning

confidence: 99%

Improving diabetic and hypertensive retinopathy with a medical food containing L-methylfolate: a preliminary report

et al. 2019

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Background Homocysteine and vitamin D may play a role in the development of diabetic and hypertensive retinopathy in patients with diabetes mellitus (DM) and hypertension. Supplementing food with L-methylfolate and vitamin D theoretically may improve diabetic and hypertensive retinopathy, however, the outcome of these nutritional approaches has not been fully examined. A retrospective case review was done of cases of retinopathy reversal in patients on Ocufolin™ and a similar nonprescription multivitamin, Eyefolate™. In this study, they were administered L-methylfolate (2.7 mg and 3.0 mg, respectively) and vitamin D3 (4500 IU each). These dosages are significantly above the RDA but well below levels associated with toxicity. Case presentation Seven patients had nonproliferative diabetic retinopathy (NPDR) and some of them had hypertension. One patient had only hypertensive retinopathy. All patients were instructed to take Ocufolin™ medical food as a food supplement. Baseline genetic testing for MTHFR polymorphisms was conducted. Fundus photography was used to document the fundus condition of the enrolled eyes in 8 NPDR patients at the initial and follow-up visits. Microaneurysms (MA) and exudates were observed to be improved in some trial patients. All subjects had one or more MTHFR polymorphisms. All had diabetic retinopathy, hypertensive retinopathy, or both. MAs were resolved, and exudates were decreased in 8/8 cases after taking the medical food. Retinal edema was found in 2/8 cases and improved or resolved in both cases after taking the medical food or the supplement. The best corrected visual activity was stable or improved in 8/8 cases. Conclusion We report a series of diabetic and hypertensive retinopathy cases with MTHFR polymorphisms and the improvement of retinal microvasculature (mainly MAs) in serial fundus photography after taking a medical food or supplement containing L-methylfolate and vitamin D. It appears that the use of nutritional supplements and medical foods containing L-methylfolate and vitamin D may be effective in facilitating the improvement of diabetic and hypertensive retinopathy.

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Lowering Homocysteine Decreases Levels and Expression of VEGF165 and Endostatin

Cited by 10 publications

References 69 publications

Homocysteine inhibits angiogenesis through cytoskeleton remodeling

Homocysteine inhibits angiogenesis through cytoskeleton remodeling

Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

Improving diabetic and hypertensive retinopathy with a medical food containing L-methylfolate: a preliminary report

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