PMID- 20581102
OWN - NLM
STAT- MEDLINE
DCOM- 20100920
LR  - 20211020
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 299
IP  - 3
DP  - 2010 Sep
TI  - Functional consequences of the collagen/elastin switch in vascular remodeling in 
      hyperhomocysteinemic wild-type, eNOS-/-, and iNOS-/- mice.
PG  - L301-11
LID - 10.1152/ajplung.00065.2010 [doi]
AB  - A decrease in vascular elasticity and an increase in pulse wave velocity in 
      hyperhomocysteinemic (HHcy) cystathionine-beta-synthase heterozygote knockout 
      (CBS(-/+)) mice has been observed. Nitric oxide (NO) is a potential regulator of 
      matrix metalloproteinase (MMP) activity in MMP-NO-tissue inhibitor of 
      metalloproteinase (TIMP) inhibitory tertiary complex. However, the contribution 
      of the nitric oxide synthase (NOS) isoforms eNOS and iNOS in the activation of 
      latent MMP is unclear. We hypothesize that 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 overall goal is to 
      elucidate the contribution of the NOS isoforms, endothelial and inducible, in the 
      collagen/elastin switch. Experiments were performed on six groups of animals 
      [wild-type (WT), eNOS(-/-), and iNOS(-/-) with and without homocysteine (Hcy) 
      treatment (0.67 g/l) for 8-12 wk]. In vivo echograph was performed to assess 
      aortic timed flow velocity for indirect compliance measurement. Histological 
      determination of collagen and elastin with trichrome and van Gieson stains, 
      respectively, was performed. In situ measurement of superoxide generation using 
      dihydroethidium was used. Differential expression of eNOS, iNOS, nitrotyrosine, 
      MMP-2 and -9, and elastin were measured by quantitative PCR and Western blot 
      analyses. The 2% gelatin zymography was used to assess MMP activity. The increase 
      in O(2)(-) and robust activity of MMP-9 in eNOS(-/-), WT+Hcy, and eNOS(-/-)+Hcy 
      was accompanied by the gross disorganization and thickening of the ECM along with 
      extensive collagen deposition and elastin degradation (collagen/elastin switch) 
      resulting in a decrease in aortic timed flow velocity. Results show that an 
      increase in iNOS activity is a key contributor to HHcy-mediated collagen/elastin 
      switch and resulting decline in aortic compliance.
FAU - Steed, Mesia M
AU  - Steed MM
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, Louisville, Kentucky 40202, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Sen, Utpal
AU  - Sen U
FAU - Schuschke, Dale A
AU  - Schuschke DA
FAU - Joshua, Irving G
AU  - Joshua IG
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-71010/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
DEP - 20100625
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-34-5 (Collagen)
RN  - 9007-58-3 (Elastin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Aorta/diagnostic imaging/*physiopathology
MH  - Blood Flow Velocity
MH  - Collagen/*metabolism
MH  - Compliance
MH  - Elastin/*metabolism
MH  - Extracellular Matrix/metabolism
MH  - Hyperhomocysteinemia/diagnostic imaging/*physiopathology
MH  - Male
MH  - Matrix Metalloproteinase 2
MH  - Matrix Metalloproteinase 9
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase Type II/deficiency/*metabolism
MH  - Nitric Oxide Synthase Type III/deficiency/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Tyrosine/analogs & derivatives/metabolism
MH  - Ultrasonography
PMC - PMC2951073
EDAT- 2010/06/29 06:00
MHDA- 2010/09/21 06:00
PMCR- 2011/09/01
CRDT- 2010/06/29 06:00
PHST- 2010/06/29 06:00 [entrez]
PHST- 2010/06/29 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - ajplung.00065.2010 [pii]
AID - L-00065-2010 [pii]
AID - 10.1152/ajplung.00065.2010 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L301-11. doi: 
      10.1152/ajplung.00065.2010. Epub 2010 Jun 25.