Methylation reactions, the redox balance and atherothrombosis: The search for a link with hydrogen sulfide

Roberta Lupoli, Alessandro Di Minno, Gaia Spadarella, Massimo Franchini, Raffaella Sorrentino, Giuseppe Cirino, Giovanni Di Minno

Research output: Contribution to journalArticlepeer-review


It is now clear that homocysteine (Hcy) is irreversibly degraded to hydrogen sulfide (H2S), an endogenous gasotransmitter that causes in vivo platelet activation via upregulation of phospholipase A2 and downstream boost of the arachidonate cascade. This mechanism involves a transsulfuration pathway. Based on these new data, clinical and experimental models on the relationships between Hcy and folate pathways in vascular disease and information on the Hcy controversy have been reanalyzed in the present review. Most interventional trials focused on Hcy lowering by folate administration did not exclude patients routinely taking the arachidonate inhibitor aspirin. This may have influenced the results of some of these trials. It is also clear that nutritional intake of folate affects several enzymatic reactions of the methionine-Hcy cycle and associated one-carbon metabolism and, thereby, both methylation reactions and redox balance. Hence, it is conceivable that the abnormally high Hcy levels seen in pathologic states reflect a poorly elucidated perturbation of such reactions and of such balance. While it is unknown whether there is an interplay between H2S, methylation reactions, and redox balance, measuring the sole reduction of blood Hcy that follows folate administration may well be an oversimplified approach to a complex biologic perturbation. The need to investigate this complex framework is thoroughly discussed in this article.

Original languageEnglish
Pages (from-to)423-432
Number of pages10
JournalSeminars in Thrombosis and Hemostasis
Issue number4
Publication statusPublished - May 14 2015


  • cell proliferation
  • epigenetics
  • inflammation
  • oxidative stress
  • translational medicine

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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