Homocysteine inhibits extra‐embryonic vascular development in the avian embryo

Latacha, Kimberly; Rosenquist, Thomas H.

doi:10.1002/dvdy.20527

Cited by 20 publications

(13 citation statements)

References 54 publications

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“…Hcy impairs the proliferation of endothelial cells in cell culture (109,144) and angiogenesis in animal models (66,96), which likely contributes to its overall impact in several vasculopathies. cbs ϩ/Ϫ mice have impaired angiogenesis, as demonstrated by the decreased compensation of blood flow and total capillary density in a hindlimb ischemia model (16).…”

Section: Impaired Angiogenesismentioning

confidence: 99%

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

Beard

Bearden

2011

American Journal of Physiology-Heart and Circulatory Physiology

106

110

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Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H(2)S) through the transsulfuration pathway. H(2)S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H(2)S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (-/-) and heterozygous (+/-), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H(2)S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease.

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Section: Impaired Angiogenesismentioning

confidence: 99%

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

Beard

Bearden

2011

American Journal of Physiology-Heart and Circulatory Physiology

106

110

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“…Despite several pathophysiological hypotheses including impaired cell proliferation, increased oxidative stress, apoptosis, reduced extra-embryonic vascular development and hypomethylation (Zetterberg, 2004;Latacha and Rosenquist, 2005), it is not clear whether hyperhomocysteinemia is causally related to REPL or whether it is only a marker of the increased risk of REPL. Actually, lowering homocysteine concentration by B-vitamin supplementation has been shown to have a positive effect in several case reports and in small series, with spontaneous pregnancies occurring after a few months of treatment in patients who had previously experienced between 4 and 12 early spontaneous abortions (Quere et al, 1998(Quere et al, , 2001Candito et al, 2003;Gueant et al, 2004).…”

Section: Folate Metabolism and Early Pregnancy Lossmentioning

confidence: 99%

Impact of folate and homocysteine metabolism on human reproductive health

Forges

Monnier‐Barbarino

Alberto

et al. 2007

Human Reproduction Update

248

188

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Folates belong to the vitamin B group and are involved in a large number of biochemical processes, particularly in the metabolism of homocysteine. Dietary or genetically determined folate deficiency leads to mild hyperhomocysteinemia, which has been associated with various pathologies. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation. Whereas the involvement of folate metabolism and homocysteine in ageing-related diseases, in several developmental abnormalities and in pregnancy complications has given rise to a large amount of scientific work, the role of these biochemical factors in the earlier stages of mammalian reproduction and the possible preventive effects of folate supplementation on fertility have, until recently, been much less investigated. In the present article, the possible roles of folates and homocysteine in male and female subfertility and related diseases are systematically reviewed, with regard to the epidemiological, pathological, pharmacological and experimental data of the literature from the last 25 years.

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“…However, there is not strong evidence of the association between folate levels in humans and risk of eye malformations (Shaw et al, 2007), with little evidence in different animal models. Armstrong and Monie (1966), after inducing maternal FA deficiency (FAD) in rats, described eye congenital defects, affecting the corneal stroma, lens, and optic cup, while an excess of homocysteine was found to cause toxic effects on the chicken (Maestro-de-las-Casas et al, 2003;Latacha and Rosenquist, 2005) and rat (Lee et al, 2007) developing eye.…”

Section: Introductionmentioning

confidence: 99%