Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.

Tsai, Jason; Wang, Hong; Perrella, Mark A.; Yoshizumi, Masao; Sibinga, Nicholas E.S.; Tan, Larissa; Haber, Edgar; Chang, Ted Hung-Tse; Schlegel, Robert; Lee, Mu En

doi:10.1172/jci118383

Cited by 188 publications

(107 citation statements)

References 35 publications

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“…Taha et al (31) suggested that Hcy induces SMC growth by a hydrogen peroxideindependent pathway, and that the effects of Hcy may combine with the known initiating events produced by oxidative stress to accelerate the progression of atherosclerosis. Tsai et al (32) showed that Hcy and serum increased DNA synthesis synergistically in both human and rat aortic SMCs.…”

Section: Discussionmentioning

confidence: 99%

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Guo

Lee

Uzui

et al. 2007

Canadian Journal of Cardiology

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Section: Discussionmentioning

confidence: 99%

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Guo

Lee

Uzui

et al. 2007

Canadian Journal of Cardiology

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“…In addition to this attack, which might be caused by homocysteinylation of the vascular wall proteins by homocysteine and/or its oxidized products (homocysteic acid, homocysteine sulfinic acid, and homocysteine thiolactone), in vitro and in vivo work suggests that reduced homocysteine can inhibit endothelial cell turn-over (Wang et al, 1997) and promote smooth muscle cell proliferation (Lubec et al, 1996b;Majors et al, 1997;Tsai et al, 1994Tsai et al, , 1996. Wang et al (1997) reported that low concentrations of homocysteine (10 to 50 mol/L) specifically inhibit the growth of endothelial cells.…”

Section: Hyperhomocysteinemia-mediated Oxidant Stress Through Imbalanmentioning

confidence: 99%

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Durand

Prost²,

Loreau

et al. 2001

Laboratory Investigation

228

147

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SUMMARY:Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N 5,10 -methylenetetrahydrofolate reductase, and vitamin B 6 deficiency, perhaps associated with cystathionine ␤-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. (Lab Invest 2001, 81:645-672).C ardiovascular diseases remain the leading cause of mortality in Western populations. Hyperlipoproteinemia, hypertension, diabetes, obesity, and tobacco smoking are the main risk factors for atherosclerosis and its thrombotic complications. However, these factors alone cannot account for all of the deaths caused by vascular pathologies.As early as 1969, clinical studies conducted in homocystinuric children revealed the importance of severe hyperhomocysteinemia in premature development of atherosclerosis and thromboembolism (McCully, 1983). According to numerous retrospective case-controlled studies, moderate increases in plasma homocysteine, which can be precisely quantitated by high performance liquid chromatography (HPLC), raise the risk for cardiovascular disease 2-fold, after adjusting for classic risk factors. Moreover, up to 20% to 40% of patients with vascular pathologies present moderate to intermediate hyperhomocysteinemia. However, results from prospective studies are inconsistent. Additionally, molecular mechanisms underlying hyperhomocysteinemia-induced vascular diseas...

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“…Specifically, cyclin D1 and cyclin A induced by growth factors or serum function as growth regulators during the early G 1 phase and S and G 2 /M phase of the cell cycle respectively (Tsai, 1996). Therefore, the interactions of homocysteine and growth factors or serum induce the replication of vascular smooth muscle cells lining the blood vessels and facilitate the mechanism for homocysteine-induced atherosclerosis (Tsai et al 1994;Tsai, 1996).…”

Section: Homocysteine and Smooth Musclementioning

confidence: 99%

Homocysteine and Malondialdehyde as Predictors of Restenosis Following Percutaneous Coronary Intervention

et al. 2006

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Restenosis is one of the major adverse outcomes of Percutaneous CoronaryIntervention (PCI). Previous studies have shown conflicting reports for homocysteine as a predictor of restenosis following PCI. The conflicting reports may be due to oxidative factors (stimulation of polymorphonuclear leukocyte [PMNL]-induced reactive oxygen species generation, xanthine-xanthine oxidase, and arachidonic acid metabolism) other than homocysteine which could cause endothelial cell dysfunction leading to restenosis.Malondialdehyde (MDA), a lipid peroxidation product, is a marker for oxidative stress and is related to all oxidative factors. Therefore, it is possible that serum MDA may be a better predictor of restenosis than plasma homocysteine. The purpose of this study is to determine whether or not the pre-procedural serum MDA and plasma homocysteine levels are elevated in patients who develop restenosis post PCI.The study included fifty-one patients undergoing elective PCI who consented to participate in a protocol that was approved by the Ethics Committee of the University of Saskatchewan. Homocysteine and malondialdehyde were measured in the plasma and serum respectively. Blood samples were collected pre-procedural, 0 time, 8 hours, 24 hours, and 6 months post-procedure. Exercise tolerance tests were performed at two weeks, and six months post-procedure to determine if there was any evidence of restenosis.The results of the study showed that pre-procedural values of plasma homocysteine in the restenosis and non-restenosis groups were 10.37 ± 0.46 and 10.73 ± 0.49 respectively. These values were not significantly different (p=0.60) between the groups. The pre-procedural levels of plasma homocysteine were not significantly ii different (p=0.08) from the post-PCI values of those patients who did not develop restenosis at the 6-month time interval. However, the pre-procedural levels of plasma homocysteine were significantly different from the post-PCI values of those patients in the restenosis group at the 24hr (p=0.04) and 6-month (p=0.002) time intervals. In the restenosis group there was a significant increase (24%) after six months in the values of homocysteine from the pre-procedural levels. Thus, this indicates that restenosis is associated with higher post-PCI levels of homocysteine.The pre-procedural levels of serum MDA in the restenosis and non-restenosis groups were 0.124± 0.16 and 0.147± 0.02 respectively. There was no significant difference (p=0.60) between the two groups. There was also no significant difference The results suggest that pre-procedural levels of plasma homocysteine and serum MDA were not predictors of restenosis following PCI. However, the post-PCI sixmonth levels of both homocysteine and MDA are predictors of restenosis. Moreover, the post-PCI levels of MDA were better predictors of restenosis than the post-PCI levels of homocysteine because the increase in MDA levels were greater at six months than the rise in homocysteine levels at the same time interval.iii ACKNOWLEDGEMENTS

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Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.

Cited by 188 publications

References 35 publications

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Homocysteine and Malondialdehyde as Predictors of Restenosis Following Percutaneous Coronary Intervention

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