PMID- 21126196
OWN - NLM
STAT- MEDLINE
DCOM- 20111201
LR  - 20220316
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 15
IP  - 7
DP  - 2011 Oct 1
TI  - Mechanisms of cardiovascular remodeling in hyperhomocysteinemia.
PG  - 1927-43
LID - 10.1089/ars.2010.3721 [doi]
AB  - In hypertension, an increase in arterial wall thickness and loss of elasticity 
      over time result in an increase in pulse wave velocity, a direct measure of 
      arterial stiffness. This change is reflected in gradual fragmentation and loss of 
      elastin fibers and accumulation of stiffer collagen fibers in the media that 
      occurs independently of atherosclerosis. Similar results are seen with an 
      elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), which 
      increases vascular thickness, elastin fragmentation, and arterial blood pressure. 
      Studies from our laboratory have demonstrated a decrease in elasticity and an 
      increase in pulse wave velocity in HHcy cystathionine beta synthase heterozygote 
      knockout (CBS(-/+)) mice. Nitric oxide (NO) is a potential regulator of matrix 
      metalloproteinase (MMP) activity in MMP-NO-TIMP (tissue inhibitor of 
      metalloproteinase) inhibitory tertiary complex. We have demonstrated the 
      contribution of the NO synthase (NOS) isoforms, endothelial NOS and inducible 
      NOS, in the activation of latent MMP. The differential production of NO 
      contributes to oxidative stress and increased oxidative/nitrative activation of 
      MMP resulting in vascular remodeling in response to HHcy. The contribution of the 
      NOS isoforms, endothelial and inducible in the collagen/elastin switch, has been 
      demonstrated. We have showed that an increase in inducible NOS activity is a key 
      contributor to HHcy-mediated collagen/elastin switch and resulting decline in 
      aortic compliance. In addition, increased levels of Hcy compete and suppress the 
      gamma-amino butyric acid-receptor, N-methyl-d-aspartate-receptor, and peroxisome 
      proliferator-activated receptor. The HHcy causes oxidative stress by generating 
      nitrotyrosine, activating the latent MMPs and decreasing the endothelial NO 
      concentration. The HHcy causes elastinolysis and decrease elastic complicance of 
      the vessel wall. The treatment with gamma-amino butyric acid-receptor agonist 
      (muscimol), N-methyl-d-aspartate-receptor antagonist (MK-801), and peroxisome 
      proliferator-activated receptor agonists (ciprofibrate and ciglitazone) mitigates 
      the cardiovascular dysfunction in HHcy [corrected].
FAU - Steed, Mesia M
AU  - Steed MM
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, 500 South Preston Street, Louisville, KY 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL 71010/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20110421
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
EIN - Antioxid Redox Signal. 2013 Feb 10;18(5):601
MH  - Animals
MH  - Cardiovascular Diseases/*etiology/metabolism
MH  - Cardiovascular System/metabolism/*pathology/physiopathology
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - Methionine/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Reactive Nitrogen Species/metabolism
MH  - Reactive Oxygen Species/metabolism
PMC - PMC3159179
EDAT- 2010/12/04 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/01
CRDT- 2010/12/04 06:00
PHST- 2010/12/04 06:00 [entrez]
PHST- 2010/12/04 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - 10.1089/ars.2010.3721 [pii]
AID - 10.1089/ars.2010.3721 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2011 Oct 1;15(7):1927-43. doi: 10.1089/ars.2010.3721. Epub 
      2011 Apr 21.