PMID- 15097236
OWN - NLM
STAT- MEDLINE
DCOM- 20041214
LR  - 20190823
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 22
IP  - 5
DP  - 2004 May
TI  - Small artery mechanics in hyperhomocysteinemic mice: effects of angiotensin II.
PG  - 959-66
AB  - OBJECTIVE: Elevated plasma homocysteine has been associated with cardiovascular 
      disease, although a causal relationship is unclear. The purpose of this study was 
      to evaluate whether mild hyperhomocysteinemia (H-Hcy) may increase vascular 
      stiffness of small arteries. METHODS: Wild-type (+/+) and heterozygous (+/-) 
      methylenetetrahydrofolate reductase (Mthfr) knockout mice, a new model of mild 
      H-Hcy, were treated with vehicle or angiotensin (Ang) II infusion (400 ng/kg per 
      min s.c.). Second-order mesenteric arteries were studied on pressurized myograph. 
      They were exposed to intraluminal pressures ranging from 3 to 140 mmHg. Media 
      thickness and lumen diameter were measured at each pressure level to determine 
      wall mechanical properties. Collagen type I/III and elastin deposition in the 
      vascular wall were evaluated by confocal immunofluorescence microscopy. RESULTS: 
      Media-to-lumen ratio was similar in Mthfr and Mthfr mice, and significantly 
      increased by Ang II. The stress-strain relationship was shifted to the left in 
      small mesenteric arteries from Mthfr compared to Mthfr mice, indicating that mild 
      H-Hcy is associated with stiffer vessels. Ang II treatment in Mthfr mice enhanced 
      the leftward shift in the stress-strain relationship and significantly increased 
      the elastic modulus, suggesting the presence of stiffer wall components in small 
      arteries in these animals. Increased collagen type I/III accumulation and 
      decreased elastin content in the media of mesenteric arteries was noted in Mthfr 
      compared to Mthfr mice. Ang II infusion augmented vascular collagen deposition in 
      both groups, more substantially in Mthfr mice. CONCLUSIONS: Mild 
      hyperhomocysteinemia is associated with stiffer small arteries with increased 
      collagen deposition in the media. These changes are accentuated by Ang II-induced 
      blood pressure elevation.
FAU - Neves, Mario F
AU  - Neves MF
AD  - Canadian Institutes of Health Research, Multidisciplinary Research Group on 
      Hypertension, Clinical Research Institute of Montreal, University of Montreal, 
      110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7.
FAU - Endemann, Dierk
AU  - Endemann D
FAU - Amiri, Farhad
AU  - Amiri F
FAU - Virdis, Agostino
AU  - Virdis A
FAU - Pu, Qian
AU  - Pu Q
FAU - Rozen, Rima
AU  - Rozen R
FAU - Schiffrin, Ernesto L
AU  - Schiffrin EL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Vasoconstrictor Agents)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9007-34-5 (Collagen)
RN  - 9007-58-3 (Elastin)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects/physiology
MH  - Collagen/metabolism
MH  - Disease Models, Animal
MH  - Elastin/metabolism
MH  - Female
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/genetics/*physiopathology
MH  - Male
MH  - Mesenteric Arteries/drug effects/metabolism/physiopathology
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Vasoconstrictor Agents/*pharmacology
EDAT- 2004/04/21 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/04/21 05:00
PHST- 2004/04/21 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/04/21 05:00 [entrez]
AID - 00004872-200405000-00018 [pii]
AID - 10.1097/00004872-200405000-00018 [doi]
PST - ppublish
SO  - J Hypertens. 2004 May;22(5):959-66. doi: 10.1097/00004872-200405000-00018.