PMID- 30781581
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20231006
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 4
DP  - 2019 Feb 17
TI  - The Contribution of Homocysteine Metabolism Disruption to Endothelial 
      Dysfunction: State-of-the-Art.
LID - 10.3390/ijms20040867 [doi]
LID - 867
AB  - Homocysteine (Hcy) is a sulfur-containing non-proteinogenic amino acid formed 
      during the metabolism of the essential amino acid methionine. Hcy is considered a 
      risk factor for atherosclerosis and cardiovascular disease (CVD), but the 
      molecular basis of these associations remains elusive. The impairment of 
      endothelial function, a key initial event in the setting of atherosclerosis and 
      CVD, is recurrently observed in hyperhomocysteinemia (HHcy). Various observations 
      may explain the vascular toxicity associated with HHcy. For instance, Hcy 
      interferes with the production of nitric oxide (NO), a gaseous master regulator 
      of endothelial homeostasis. Moreover, Hcy deregulates the signaling pathways 
      associated with another essential endothelial gasotransmitter: hydrogen sulfide. 
      Hcy also mediates the loss of critical endothelial antioxidant systems and 
      increases the intracellular concentration of reactive oxygen species (ROS) 
      yielding oxidative stress. ROS disturb lipoprotein metabolism, contributing to 
      the growth of atherosclerotic vascular lesions. Moreover, excess Hcy maybe be 
      indirectly incorporated into proteins, a process referred to as protein 
      N-homocysteinylation, inducing vascular damage. Lastly, cellular hypomethylation 
      caused by build-up of S-adenosylhomocysteine (AdoHcy) also contributes to the 
      molecular basis of Hcy-induced vascular toxicity, a mechanism that has merited 
      our attention in particular. AdoHcy is the metabolic precursor of Hcy, which 
      accumulates in the setting of HHcy and is a negative regulator of most cell 
      methyltransferases. In this review, we examine the biosynthesis and catabolism of 
      Hcy and critically revise recent findings linking disruption of this metabolism 
      and endothelial dysfunction, emphasizing the impact of HHcy on endothelial cell 
      methylation status.
FAU - Esse, Ruben
AU  - Esse R
AD  - Department of Biochemistry, Boston University School of Medicine, Boston, MA 
      02118, USA. ruben.esse@gmail.com.
FAU - Barroso, Madalena
AU  - Barroso M
AUID- ORCID: 0000-0002-1600-890X
AD  - University Children's Research@Kinder-UKE, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany. m.barroso@uke.de.
FAU - Tavares de Almeida, Isabel
AU  - Tavares de Almeida I
AD  - Laboratory of Metabolism and Genetics, Faculty of Pharmacy, University of Lisbon, 
      1649-003 Lisbon, Portugal. italmeida@ff.ul.pt.
FAU - Castro, Rita
AU  - Castro R
AUID- ORCID: 0000-0002-4585-0741
AD  - Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of 
      Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal. mum689@psu.edu.
AD  - Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of 
      Lisbon, 1649-003 Lisbon, Portugal. mum689@psu.edu.
AD  - Department of Nutritional Sciences, The Pennsylvania State University, University 
      Park, PA 16802, USA. mum689@psu.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - AE28F7PNPL (Methionine)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Atherosclerosis/*metabolism/pathology
MH  - Cardiovascular Diseases/*metabolism/pathology
MH  - Endothelial Cells/metabolism/pathology
MH  - Homocysteine/*metabolism/toxicity
MH  - Humans
MH  - Hydrogen Sulfide/metabolism
MH  - Hyperhomocysteinemia/*metabolism/pathology
MH  - Methionine/metabolism
MH  - Nitric Oxide/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - S-Adenosylhomocysteine/metabolism
PMC - PMC6412520
OTO - NOTNLM
OT  - S-adenosylhomocysteine
OT  - atherosclerosis
OT  - cellular methylation
COIS- The authors declare no conflict of interest.
EDAT- 2019/02/20 06:00
MHDA- 2019/05/30 06:00
PMCR- 2019/02/01
CRDT- 2019/02/21 06:00
PHST- 2019/01/18 00:00 [received]
PHST- 2019/02/05 00:00 [revised]
PHST- 2019/02/12 00:00 [accepted]
PHST- 2019/02/21 06:00 [entrez]
PHST- 2019/02/20 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2019/02/01 00:00 [pmc-release]
AID - ijms20040867 [pii]
AID - ijms-20-00867 [pii]
AID - 10.3390/ijms20040867 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Feb 17;20(4):867. doi: 10.3390/ijms20040867.