Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension

Catena, Cristiana; Colussi, GianLuca; Url–Michitsch, Marion; Nait, Francesca; Sechi, Leonardo A.

doi:10.1016/j.jash.2014.12.020

Cited by 36 publications

(19 citation statements)

References 43 publications

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“…We propose that this mechanism has strong implications for immunosuppression, and particularly for patients with cardiovascular diseases and severe hyperhomocysteinaemia that was shown to be associated with inflammation and cardiovascular complications. Our findings may provide clues to explain why hyperhomocysteinaemia constitutes a risk factor in cardiovascular diseases and may therefore help to define new therapeutic strategies.…”

Section: Discussionmentioning

confidence: 88%

High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability

Bruzzese

Fenouillet

Fromonot

et al. 2016

J Cellular Molecular Medi

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High homocysteine (HCy) levels are associated with lymphocyte‐mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia‐induced, adenosine‐mediated, alteration of lymphocyte viability. We treated mitogen‐stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T‐cell line CEM with cobalt chloride (CoCl2)to reproduce hypoxia. We found that CoCl2‐altered cell viability was dose‐dependently reversed using HCy. In turn, the HCy effect was inhibited using DL‐propargylglycine, a specific inhibitor of the hydrogen sulphide (H2S)‐synthesizing enzyme cystathionine‐γ‐lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 AR). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 AR expression and 3′, 5′‐cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia‐induced adenosinergic signalling despite high adenosine concentration by promoting both S‐adenosylhomocysteine and H2S production; (iii) DL‐propargylglycine that inhibits H2S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2S production and the resulting down‐regulation of A2 AR expression, the hypoxia‐induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 88%

High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability

Bruzzese

Fenouillet

Fromonot

et al. 2016

J Cellular Molecular Medi

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“…Specific targets to increase the availability of methyl donor include acceleration of the conversion from homocysteine to methionine. Abnormally high levels of homocysteine have been reported to be a significant risk factor for the development of a wide range of diseases such as in cerebrovascular diseases [ 241 , 242 , 243 , 244 ], various CVDs [ 245 , 246 , 247 , 248 , 249 ], cognitive impairment including Alzheimer’s disease [ 250 , 251 , 252 ], fractures [ 253 , 254 , 255 ], and mortality [ 256 ]. Deficiencies of vitamin B12, folate, or vitamin B6 seem to play an important role in the occurrence of hyperhomocysteinemia, because they are essential for homocysteine metabolism ( Figure 2 ), and treatment with B-vitamin supplementation (B6, B12, and folate) has been demonstrated to effectively lower homocysteine levels [ 257 , 258 , 259 , 260 , 261 ].…”

Section: Nutrients and Their Metabolites And Enzymes Related To Dnmentioning

confidence: 99%

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Soda

2018

IJMS

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Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

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“…Age, sex, being overweight/obesity, sodium intake, tobacco use, alcohol consumption, and dyslipidemia are well‐established traditional predisposing factors for hypertension . Elevated plasma homocysteine levels (hyperhomocysteinemia, defined as plasma homocysteine concentrations ≥10 μmol/L) is an independent risk factor for cardiovascular diseases . Our previous meta‐analysis showed that the prevalence of hyperhomocysteinemia in China was 27.5%, and was higher in northerners, the inlanders, men, and the elderly .…”

Section: Introductionmentioning

confidence: 99%

Interactions of homocysteine and conventional predisposing factors on hypertension in Chinese adults

Yang

Fan

Zhi

et al. 2017

J of Clinical Hypertension

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This study aimed to investigate whether conventional predisposing factors modify the associations of homocysteine with blood pressure levels and hypertension. A total of 2615 adults were recruited from Liaoning province. An elevated homocysteine level was significantly associated with increased hypertension risk and blood pressure (all P<.05). Interaction analyses showed that homocysteine acted synergistically with age, overweight/obesity, dyslipidemia, and family history of hypertension to affect hypertension risk, and the relative excess risk due to interaction was 1.21 (95% confidence interval, 0.07–2.35), 0.72 (95% confidence interval, 0.07–1.36), 0.45 (95% confidence interval, 0.06–0.85), and 1.87 (95% confidence interval, 0.77–2.97), respectively. Increases in blood pressure were higher in patients who were overweight/obese or had a family history of hypertension than in their counterparts (all Pinteraction <.05). This study provides some strong evidence for interactions of homocysteine with conventional predisposing factors on hypertension.

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Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension

Cited by 36 publications

References 43 publications

High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability

High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Interactions of homocysteine and conventional predisposing factors on hypertension in Chinese adults

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Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension

Cited by 36 publications

References 43 publications

High homocysteine levels prevent via H2S the CoCl2‐induced alteration of lymphocyte viability

High homocysteine levels prevent via H2S the CoCl2‐induced alteration of lymphocyte viability

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Interactions of homocysteine and conventional predisposing factors on hypertension in Chinese adults

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Product

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High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability

High homocysteine levels prevent via H₂S the CoCl₂‐induced alteration of lymphocyte viability