Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 μmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.
Homocysteine ; Humans ; Hyperhomocysteinemia ; complications ; Kidney Diseases ; complications

Hypercoagulability state is the result of the interplay of genetic predisposition and risk factors. Many key enzymes and reactions in coagulation and anti-coagulation system are involved. Hereditary antithrombin deficiency is one of the major risk factors of venous thromboembolic disease (VTE), whereas hyperhomocysteinemia may also play a role. This article reviews the recent researches on the contributions of these two factors to VTE.
Antithrombin III Deficiency ; complications ; Humans ; Hyperhomocysteinemia ; complications ; Venous Thrombosis ; etiology

A case of combined methylmalonic aciduria and homocysteinemia presenting with hydrocephalus as an early manifestation was reported for its rarity to see and to discuss the relationship between metabolic diseases and hydrocephalus by literature review. The case was an infant with seizures and hydrocephalus as an early manifestation of the disease, combined with macrocyticanemia, development retardation and visual hearing function lesions. The EEG showed hypsarrhythmia and the MRI showed hydrocephalus. Plasma homocysteinemia level increased (143.06 umol/L) and urine methylmalonic aciduria was 1483 times beyond normal. Based on gene analysis results and increased methylmalonic aciduria and homocysteinemia levels, combined methylmalonic aciduria and homocysteinemia was confirmed, presenting CblC defect (gene mutations homozygous for c.609G>A). After treatment by venous injection of vitamin B12, oral folic acid and betaine, seizures were controlled and development was progressive with ventricle retraction. It was concluded that hydrocephalus can be the early presentation in children with combined methylmalonic aciduria and homocysteinemia. Doctors should carry out metabolic disease screening for patients with hydrocephalus, especially when the cause of hydrocephalus is uncertain.
Amino Acid Metabolism, Inborn Errors ; complications ; Humans ; Hydrocephalus ; etiology ; Hyperhomocysteinemia ; complications ; Infant ; Male

Hyperhomocysteinemia (HHcy) has been recognized as an independent risk factor for atherosclerosis for more than 30 years, but the mechanisms by which HHcy leads to atherosclerosis are not well fully understood. In this review, we will summarize the immunoregulatory effects of homocysteine on cardiovascular diseases from humoral immunity, monocyte/macrophage and T lymphocyte activity. Homocysteine can induce chemokine and cytokine secretion in monocytes and T lymphocytes and also directly stimulate B lymphocyte proliferation and IgG secretion. In addition, the cellular mechanisms that may explain the pro-inflammatory effect of HHcy are included. Homocysteine may directly or indirectly lead to oxidative stress or endoplasmic reticulum (ER) stress. Elevated levels of homocysteine also decrease the bioavailability of nitric oxide and modulate the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular diseases.
Animals ; Atherosclerosis ; Cardiovascular Diseases ; immunology ; physiopathology ; Homocysteine ; physiology ; Humans ; Hyperhomocysteinemia ; complications ; Macrophages ; Nitric Oxide ; Oxidative Stress

OBJECTIVETo observe the correlation between the decline of cognitive function and the level of plasma homocysteine in patients with Alzheimer's disease (AD).

METHODSThirty six AD patients were selected from hospitals in Tianjin. The enrolled patients were in accord with the diagnosis criteria. Thirty two control subjects were corresponding patients without AD in the period. Blood samples were extracted from each subject to determine the levels of homocysteine (Hcy) and folate. Cognitive status was evaluated by the mini- mental state examination (MMSE) and clinical dementia rating scale (CDR).

RESULTSThe mean value of serum Hcy concentration [(17.51 +/- 5.62) micromol/L] of AD group was higher than that of control group [(12.38 +/- 4.25)micromol/L]. The serum [(5.17 +/- 1.76) microg/L] and diet folate [(206.94 +/- 44.51) microg/d] concentration of AD group were lower than those of control group [(7.92 +/- 2.22) microg/L, (259.74 +/- 41.92) microg/ d]. The incidence of hyperhomocysteinemia in AD group (64%) was higher than that in control group (22%). A significant relation between Hcy concentrations and the CDR was observed. With the increase of Hcy concentrations the CDR raised, and with the increase of Hcy concentrations the MMSE decreased.

CONCLUSIONHyperhomocysteinemia is one of the risk factors inducing the onset of AD. There is a significant negative correlation between Hcy levels and cognitive levels in AD group. Folate deficiency is an important reason to cause elevated Hcy levels in AD.

Alzheimer Disease ; blood ; etiology ; Case-Control Studies ; Folic Acid ; blood ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; blood ; complications

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.
Humans ; Atherosclerosis ; Cardiovascular Diseases ; Endothelium, Vascular ; Homocysteine/metabolism* ; Hyperhomocysteinemia/complications* ; Oxidative Stress ; Risk Factors

Objective To explore the association between plasma homocysteine (Hcy) level and hyper-uricemia (HUA) in the elderly patients with hypertension.Methods From March to August in 2018,9902 hypertensive patients ≥ 60 years were routinely tested for blood biochemical indicators in Wuyuan county,Jiangxi province.The patients were assigned into a HUA group and a normal uric acid group.Multivariate Logistic regression was adopted to analyze the relationship between Hcy level and the risk of HUA.Results Compared with the normal uric acid group,the HUA group showed increased incidence of hyperhomocysteinemia (99.9% vs.98.7%,P<0.001) and elevated Hcy level[16.8 (13.8-21.5) μmol/L vs.14.4 (12.3-17.7) μmol/L,P<0.001].The multivariate Logistic regression analysis showed that after adjusting for influencing factors,the risk of HUA in the patients with hyperhomocysteinemia was 2.92 times of that in the patients with a normal Hcy level.The threshold effect analysis showed that the Hcy level was positively correlated with the occurrence of HUA in the case of Hcy<20 μmol/L (OR=1.05,95%CI=1.04-1.07,P<0.001).In the case of Hcy ≥ 20 μmol/L,there was no correlation between Hcy level and HUA (OR=1.00,95%CI=0.99-1.00,P=0.055),and the likelihood ratio test showed statistically significant results (P<0.001).Conclusion The elderly with hypertension should pay attention to control the Hcy level,which will be helpful to prevent the occurrence of HUA.
Humans ; Aged ; Hyperuricemia/complications* ; Hyperhomocysteinemia/epidemiology* ; Uric Acid ; Hypertension ; Homocysteine ; Risk Factors

OBJECTIVETo study the relationship between the plasma homocysteine (HCY) level and the polymorphism of N(5), N(10)-methylenetetrahydrofolate reductase (MTHFR) gene C667T in liver cirrhosis.

METHODS112 normal subjects and 87 liver cirrhosis patients were recruited in the study. Their plasma HCY levels were measured using high performance liquid chromatography with fluorescence detection and polymorphisms of their MTHFR gene were analyzed using PCR-RFLP.

RESULTSThe mean level of plasma HCY was significantly higher in patients with liver cirrhosis (21.71+/-4.86) micromol/L than that in healthy individuals (8.34+/-3.59) micromol/L. There were three kinds of MTHFR genotypes: +/+ (TT, homozygous mutation), +/- (CT, heterozygous mutation) and -/- (CC, wild type). The frequencies of the three genotypes were as follows: +/+, 29.9%; +/-, 52.9%; -/-, 17.2% in cirrhosis patients and +/+, 19.6%; +/-, 33.9%; -/-, 46.4% in normal subjects. The frequency of homozygous or heterozygous mutation was significantly higher in cirrhosis patients than that in the normal control. Moreover, plasma homocysteine level was markedly higher in patients with MTHFR genetic mutation than those without mutation.

CONCLUSIONSHyperhomocysteinemia may be an independent risk factor for liver cirrhosis. MTHFR is the main enzyme related to homocysteine metabolism. The genetic mutation of MTHFR C667T is possibly an important mechanism of hyperhomocysteinemia in liver cirrhosis. The level of plasma homocysteine may be an early indicator for liver cirrhosis.

Female ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; complications ; genetics ; Liver Cirrhosis ; complications ; genetics ; Male ; Methylenetetrahydrofolate Dehydrogenase (NAD+) ; genetics ; Point Mutation ; Polymorphism, Genetic

To investigate the effect of stress on homocysteine metabolism in the rat and explore the mechanism as well as the key regulatory link of stress-induced hyperhomocysteinemia, male Wistar rats were treated with restraint stress while control rats received routine treatment. By HPLC-fluorometry, the homocysteine level in rat plasma was determined. Cystathionine beta-synthase (CBS) activity in blood, heart, liver and kidney was measured by radioisotope assay using [(14)C]-serine as the labeled substrate. Total RNA was isolated from rat liver after restraint stress. RT-PCR and Northern blot were used to estimate the level of CBS mRNA. The results showed that hyperhomocysteinemia was induced by restraint stress. The highest CBS enzyme activity was seen in rat livers. A decrease in hepatic activities of CBS was found in restraint stress rats. The 29.4% +/-2.5% reduction in the activity of CBS was accompanied by a 44.1% +/-3.4% decrease in its mRNA level. CBS enzyme activity was slightly elevated in the kidney of stressed rats while it was almost undeterminable in the cardiovascular system. The study suggests that stress leads to an inhibition of the transsulfuration pathway in homocysteine metabolism. The hepatic CBS influenced by stress at the level of transcription exerts a profound effect on the circulating levels of homocysteine. The liver is the key organ where stress affects homocysteine metabolism.
Animals ; Down-Regulation ; Homocysteine ; metabolism ; Hyperhomocysteinemia ; blood ; etiology ; Male ; Rats ; Rats, Wistar ; Restraint, Physical ; Stress, Physiological ; complications ; metabolism

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cognitive Dysfunction/complications* ; DNA Methylation ; Homocysteine/metabolism* ; Hyperhomocysteinemia/metabolism* ; Rats ; Stress, Psychological/physiopathology*