PMID- 20971760
OWN - NLM
STAT- MEDLINE
DCOM- 20110128
LR  - 20240420
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 300
IP  - 1
DP  - 2011 Jan
TI  - Vascular complications of cystathionine beta-synthase deficiency: future directions 
      for homocysteine-to-hydrogen sulfide research.
PG  - H13-26
LID - 10.1152/ajpheart.00598.2010 [doi]
AB  - Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is 
      converted to hydrogen sulfide (H(2)S) through the transsulfuration pathway. H(2)S 
      has attracted considerable attention in recent years for many positive effects on 
      vascular health and homeostasis. Cystathionine beta-synthase (CBS) is the first, and 
      rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene 
      decrease enzymatic activity, which increases the plasma Hcy concentration, a 
      condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency 
      have provided invaluable insights into the pathological effects of 
      transsulfuration impairment and of both mild and severe HHcy. However, studies 
      have also highlighted the complexity of HHcy and the need to explore the specific 
      details of Hcy metabolism in addition to Hcy levels per se. There has been a 
      relative paucity of work addressing the dysfunctional H(2)S production in CBS 
      deficiency that may contribute to, or even create, HHcy-associated pathologies. 
      Experiments using CBS knockout mice, both homozygous (-/-) and heterozygous 
      (+/-), have provided 15 years of new knowledge and are the focus of this review. 
      These murine models present the opportunity to study a specific mechanism for 
      HHcy that matches one of the etiologies in many human patients. Therefore, the 
      goal of this review was to integrate and highlight the critical information 
      gained thus far from models of CBS deficiency and draw attention to critical gaps 
      in knowledge, with particular emphasis on the modulation of H(2)S metabolism. We 
      include findings from human and animal studies to identify important 
      opportunities for future investigation that should be aimed at generating new 
      basic and clinical understanding of the role of CBS and transsulfuration in 
      cardiovascular and neurovascular disease.
FAU - Beard, Richard S Jr
AU  - Beard RS Jr
AD  - Department of Biological Sciences, Idaho State University, Pocatello, Idaho ID 
      83209-8007, USA.
FAU - Bearden, Shawn E
AU  - Bearden SE
LA  - eng
GR  - P20-RR-016454/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20101022
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Homocysteine/*metabolism
MH  - Homocystinuria/*complications/metabolism
MH  - Humans
MH  - Hydrogen Sulfide/*metabolism
MH  - Mice
MH  - Vascular Diseases/*etiology/metabolism
PMC - PMC3023265
EDAT- 2010/10/26 06:00
MHDA- 2011/02/01 06:00
PMCR- 2012/01/01
CRDT- 2010/10/26 06:00
PHST- 2010/10/26 06:00 [entrez]
PHST- 2010/10/26 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - ajpheart.00598.2010 [pii]
AID - H-00598-2010 [pii]
AID - 10.1152/ajpheart.00598.2010 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H13-26. doi: 
      10.1152/ajpheart.00598.2010. Epub 2010 Oct 22.