PMID- 21161416
OWN - NLM
STAT- MEDLINE
DCOM- 20110428
LR  - 20240412
IS  - 1689-1392 (Electronic)
IS  - 1425-8153 (Print)
IS  - 1425-8153 (Linking)
VI  - 16
IP  - 1
DP  - 2011 Mar
TI  - Endothelial microparticle formation in moderate concentrations of homocysteine 
      and methionine in vitro.
PG  - 69-78
LID - 10.2478/s11658-010-0040-2 [doi]
AB  - Microparticles (MPs) are small membrane vesicles released by stimulated or 
      apoptotic cells, including the endothelium. Hyperhomocysteinemia (HHcy) is a 
      blood disorder characterized by an increase in the plasma concentrations of total 
      homocysteine (Hcy). The plasma Hcy level is determined by environmental factors 
      (dietary habits, i.e. the intake of folic acid, FA) and genetic factors (N (5),N 
      (10)-methylenetetrahydro-folate reductase, MTHFR, polymorphism 677C>T). To 
      evaluate whether moderate Hcy concentrations induce endothelial MP formation, the 
      role of FA supplementation and the influence of MTHFR polymorphism were analysed. 
      Human umbilical vein endothelial cells (HUVEC) were treated in vitro with 50 muM 
      of Hcy and methionine (Met). The MP number and apoptotic phenotype were analyzed 
      using flow cytometry. Increasing doses of FA (5, 15 and 50 muM) were used to 
      reduce the HHcy effect. The MTHFR 677C>T polymorphism was determined. HUVEC 
      stimulated by Hcy produced significantly more MPs than HUVEC under the control 
      conditions: 3,551 +/- 620 vs 2,270 +/- 657 kMP (p = 0.02). Supplementation with FA at 
      concentrations of 5, 15 and 50 muM reduced the MP count in the cell culture 
      supernatant to 345 +/- 332, 873 +/- 329, and 688 +/- 453 kMP, respectively (p = 0.03). 
      MTHFR 677C>T heterozygosity was associated with a significant increase in MP 
      formation after stimulation with Hcy compared to the control conditions: 3,617 +/- 
      152 vs 1,518 +/- 343 kMP (p = 0.02). Furthermore, the MTHFR genotype altered MP 
      formation after Met loading. On average, 24% of the entire MP population was 
      apoptotic (annexin V-positive). Endothelial function impairment due to HHcy is 
      related to MP shedding, which may involve platelets and other blood and vascular 
      cells. MP shedding is a physiological response to moderate HHcy.
FAU - Sekula, Malgorzata
AU  - Sekula M
AD  - Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
FAU - Janawa, Greta
AU  - Janawa G
FAU - Stankiewicz, Elzbieta
AU  - Stankiewicz E
FAU - Stepien, Ewa
AU  - Stepien E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101215
PL  - England
TA  - Cell Mol Biol Lett
JT  - Cellular & molecular biology letters
JID - 9607427
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 935E97BOY8 (Folic Acid)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Apoptosis
MH  - Cell-Derived Microparticles/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Endothelium, Vascular/cytology
MH  - Flow Cytometry
MH  - Folic Acid/pharmacology
MH  - Genotype
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Methionine/*pharmacology
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Umbilical Cord/cytology
PMC - PMC6275923
EDAT- 2010/12/17 06:00
MHDA- 2011/04/29 06:00
PMCR- 2010/12/15
CRDT- 2010/12/17 06:00
PHST- 2010/08/30 00:00 [received]
PHST- 2010/12/01 00:00 [accepted]
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/04/29 06:00 [medline]
PHST- 2010/12/15 00:00 [pmc-release]
AID - 40 [pii]
AID - 10.2478/s11658-010-0040-2 [doi]
PST - ppublish
SO  - Cell Mol Biol Lett. 2011 Mar;16(1):69-78. doi: 10.2478/s11658-010-0040-2. Epub 
      2010 Dec 15.