PMID- 34205914
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210714
IS  - 2218-1989 (Print)
IS  - 2218-1989 (Electronic)
IS  - 2218-1989 (Linking)
VI  - 11
IP  - 6
DP  - 2021 Jun 1
TI  - Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood 
      Clots.
LID - 10.3390/metabo11060354 [doi]
LID - 354
AB  - Hyperhomocysteinemia (HHcy) is associated with thrombosis, but the mechanistic 
      links between them are not understood. We studied effects of homocysteine (Hcy) 
      on clot contraction in vitro and in a rat model of HHcy. Incubation of blood with 
      exogenous Hcy for 1 min enhanced clot contraction, while 15-min incubation led to 
      a dose-dependent suppression of contraction. These effects were likely due to 
      direct Hcy-induced platelet activation followed by exhaustion, as revealed by an 
      increase in fibrinogen-binding capacity and P-selectin expression determined by 
      flow cytometry. In the blood of rats with HHcy, clot contraction was enhanced at 
      moderately elevated Hcy levels (10-50 muM), while at higher Hcy levels (>50 muM), 
      the onset of clot contraction was delayed. HHcy was associated with 
      thrombocytosis combined with a reduced erythrocyte count and hypofibrinogenemia. 
      These data suggest that in HHcy, platelets get activated directly and indirectly, 
      leading to enhanced clot contraction that is facilitated by the reduced content 
      and resilience of fibrin and erythrocytes in the clot. The excessive platelet 
      activation can lead to exhaustion and impaired contractility, which makes clots 
      larger and more obstructive. In conclusion, HHcy modulates blood clot 
      contraction, which may comprise an underappreciated pro- or antithrombotic 
      mechanism.
FAU - Litvinov, Rustem I
AU  - Litvinov RI
AUID- ORCID: 0000-0003-0643-1496
AD  - Department of Cell and Developmental Biology, University of Pennsylvania School 
      of Medicine, Philadelphia, PA 19104, USA.
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Peshkova, Alina D
AU  - Peshkova AD
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Le Minh, Giang
AU  - Le Minh G
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Khaertdinov, Nail N
AU  - Khaertdinov NN
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Evtugina, Natalia G
AU  - Evtugina NG
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Sitdikova, Guzel F
AU  - Sitdikova GF
AUID- ORCID: 0000-0001-5412-2204
AD  - Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 
      Kazan, Russia.
FAU - Weisel, John W
AU  - Weisel JW
AD  - Department of Cell and Developmental Biology, University of Pennsylvania School 
      of Medicine, Philadelphia, PA 19104, USA.
LA  - eng
GR  - HL148227, HL148014/NH/NIH HHS/United States
GR  - 20-15-00100/Russian Science Foundation/
PT  - Journal Article
DEP - 20210601
PL  - Switzerland
TA  - Metabolites
JT  - Metabolites
JID - 101578790
PMC - PMC8228611
OTO - NOTNLM
OT  - blood clotting
OT  - contraction of blood clots
OT  - homocysteine
OT  - hyperhomocysteinemia
OT  - platelets
OT  - retraction of blood clots
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/03 06:00
MHDA- 2021/07/03 06:01
PMCR- 2021/06/01
CRDT- 2021/07/02 01:26
PHST- 2021/04/07 00:00 [received]
PHST- 2021/05/21 00:00 [revised]
PHST- 2021/05/30 00:00 [accepted]
PHST- 2021/07/02 01:26 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/03 06:01 [medline]
PHST- 2021/06/01 00:00 [pmc-release]
AID - metabo11060354 [pii]
AID - metabolites-11-00354 [pii]
AID - 10.3390/metabo11060354 [doi]
PST - epublish
SO  - Metabolites. 2021 Jun 1;11(6):354. doi: 10.3390/metabo11060354.