Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension

Abstract

Over the past several years, hydrogen sulfide (H2S) has been shown to be an important player in a variety of physiological functions, including neuromodulation, vasodilation, oxidant regulation, inflammation, and angiogenesis. H2S is synthesized primarily through metabolic processes from the amino acid cysteine and homocysteine in various organ systems including neuronal, cardiovascular, gastrointestinal, and kidney. Derangement of cysteine and homocysteine metabolism and clearance, particularly in the renal vasculature, leads to H2S biosynthesis deregulation causing or contributing to existing high blood pressure. While a variety of environmental influences, such as diet can have an effect on H2S regulation and function, genetic factors, and more recently epigenetics, also have a vital role in H2S regulation and function, and therefore disease initiation and progression. In addition, new research into the role of gut microbiota in the development of hypertension has highlighted the need to further explore these microorganisms and how they influence the levels of H2S throughout the body and possibly exploiting microbiota for use of hypertension treatment. In this review, we summarize recent advances in the field of hypertension research emphasizing renal contribution and how H2S physiology can be exploited as a possible therapeutic strategy to ameliorate kidney dysfunction as well as to control blood pressure.

New Progress regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on <i>Lactobacillus</i> Species

“…Several animal and human studies have observed the association between the oral and gut microbiome with blood pressure [68]. The study confirmed a considerable reduction in microbial richness and multiplicity in the presence of hypertension.…”

Faulty homocysteine recycling in diabetic retinopathy

“…Homocysteine formed can either be remethylated back to L-methionine, or via transsulfuration, to L-cysteine, and cysteine is an important amino acid for the biosynthesis of glutathione (GSH). Enzymatically, methylenetetrahydrofolate reductase (MTHFR) converts homocysteine to methionine, and CBS catalyzes the condensation of homocysteine with serine to form cystathionine, which can be further converted to L-cysteine [15][16][17]. In addition to cysteine being a substrate for the biosynthesis of glutathione, it also serves as a substrate for CBS and cystathionine-γ lyase (CSE) to produce hydrogen sulfide (H 2 S) via a desulfuration reaction [16].…”

Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug targets

“…Third, homocysteine is metabolized to form Cys via trans‐sulphuration, sequentially catalysed by the vitamin B6‐dependent enzymes cystathionine β‐synthase (CBS) and cystathionine γ‐lyase (CSE) (Skovierova et al ., ). These trans‐sulphuration enzymes CBS and CSE, exhibit other enzymic activities that contribute to the biosynthesis of the gasotransmitter H 2 S, from homocysteine and/or Cys (Weber et al ., ). Deficiencies in re‐methylation and trans‐sulphuration are the main causes of the accumulation of homocysteine (Figure ).…”