PMID- 28836260
OWN - NLM
STAT- MEDLINE
DCOM- 20190607
LR  - 20220409
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 175
IP  - 8
DP  - 2018 Apr
TI  - Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug 
      targets.
PG  - 1173-1189
LID - 10.1111/bph.13988 [doi]
AB  - Homocysteine is a sulphur-containing non-proteinogenic amino acid. 
      Hyperhomocysteinaemia (HHcy), the pathogenic elevation of plasma homocysteine as 
      a result of an imbalance of its metabolism, is an independent risk factor for 
      various vascular diseases, such as atherosclerosis, hypertension, vascular 
      calcification and aneurysm. Treatments aimed at lowering plasma homocysteine via 
      dietary supplementation with folic acids and vitamin B are more effective in 
      preventing vascular disease where the population has a normally low folate 
      consumption than in areas with higher dietary folate. To date, the mechanisms of 
      HHcy-induced vascular injury are not fully understood. HHcy increases oxidative 
      stress and its downstream signalling pathways, resulting in vascular 
      inflammation. HHcy also causes vascular injury via endoplasmic reticulum stress. 
      Moreover, HHcy up-regulates pathogenic genes and down-regulates protective genes 
      via DNA demethylation and methylation respectively. Homocysteinylation of 
      proteins induced by homocysteine also contributes to vascular injury by 
      modulating intracellular redox state and altering protein function. Furthermore, 
      HHcy-induced vascular injury leads to neuronal damage and disease. Also, an 
      HHcy-activated sympathetic system and HHcy-injured adipose tissue also cause 
      vascular injury, thus demonstrating the interactions between the organs injured 
      by HHcy. Here, we have summarized the recent developments in the mechanisms of 
      HHcy-induced vascular injury, which are further considered as potential 
      therapeutic targets in this condition. LINKED ARTICLES: This article is part of a 
      themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To 
      view the other articles in this section visit 
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
CI  - (c) 2017 The British Pharmacological Society.
FAU - Fu, Yi
AU  - Fu Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Health Science Center, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
FAU - Wang, Xian
AU  - Wang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Health Science Center, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
FAU - Kong, Wei
AU  - Kong W
AUID- ORCID: 0000-0001-6720-6810
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Health Science Center, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170922
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/metabolism
MH  - Vascular System Injuries/*etiology/metabolism
PMC - PMC5867019
EDAT- 2017/08/25 06:00
MHDA- 2019/06/08 06:00
PMCR- 2019/04/01
CRDT- 2017/08/25 06:00
PHST- 2017/02/17 00:00 [received]
PHST- 2017/07/27 00:00 [revised]
PHST- 2017/08/12 00:00 [accepted]
PHST- 2017/08/25 06:00 [pubmed]
PHST- 2019/06/08 06:00 [medline]
PHST- 2017/08/25 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - BPH13988 [pii]
AID - 10.1111/bph.13988 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2018 Apr;175(8):1173-1189. doi: 10.1111/bph.13988. Epub 2017 Sep 
      22.