Abstract
Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. Platelets play an important role in cardiovascular disease and release pro-aggregates mediators when activated, such as ADP, a physiological agonist involved in normal hemostasis and thrombosis. NTPDases and 5'-nucleotidase are ecto-enzymes that hydrolyze ATP, ADP and AMP to adenosine playing an important role on blood flow and thrombogenesis by regulating ADP catabolism. The aim of the present study was evaluate extracellular adenine nucleotide hydrolysis of rat platelets exposed to homocysteine in vitro and in vivo. In vitro homocysteine (Hcy) in the concentration range of 20 to 500 μM caused a significant decrease on ATP (around 30%) and ADP (around 45%) hydrolysis, respectively, while AMP hydrolysis was not altered. Hcy was not able to inhibit the hydrolysis of ATP and ADP catalyzed by purified apyrase at the same concentrations tested in vitro on platelets, suggesting an indirect effect. The inhibitory effect of Hcy on platelets was prevented by antioxidants agents in vitro and in vivo. Furthermore homocysteine treatment increased platelet aggregation induced by ADP. Based on the results presented herein, we propose that inhibition of extracellular ATP and ADP hydrolysis caused by homocysteine was probably due oxidative stress, since antioxidants prevented such effects. These findings may contribute to an increase platelet response to ADP and consequence development of thrombotic risk attributed to hyperhomocysteinemia.
Original language | English |
---|---|
Journal | Thrombosis Research |
Volume | 125 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2010 |
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Keywords
- ADP
- ATP
- Homocysteine
- NTPDase
- Platelet
ASJC Scopus subject areas
- Medicine(all)
- Hematology
Cite this
Homocysteine decreases extracellular nucleotide hydrolysis in rat platelets. / Fernandes Zanin, Rafael; Ingrassia Campesato, Luís Felipe; Braganhol, Elizandra; Chitolina Schetinger, Maria Rosa; de Souza Wyse, Angela Terezinha; Oliveira Battastini, Ana Maria.
In: Thrombosis Research, Vol. 125, No. 3, 03.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Homocysteine decreases extracellular nucleotide hydrolysis in rat platelets
AU - Fernandes Zanin, Rafael
AU - Ingrassia Campesato, Luís Felipe
AU - Braganhol, Elizandra
AU - Chitolina Schetinger, Maria Rosa
AU - de Souza Wyse, Angela Terezinha
AU - Oliveira Battastini, Ana Maria
PY - 2010/3
Y1 - 2010/3
N2 - Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. Platelets play an important role in cardiovascular disease and release pro-aggregates mediators when activated, such as ADP, a physiological agonist involved in normal hemostasis and thrombosis. NTPDases and 5'-nucleotidase are ecto-enzymes that hydrolyze ATP, ADP and AMP to adenosine playing an important role on blood flow and thrombogenesis by regulating ADP catabolism. The aim of the present study was evaluate extracellular adenine nucleotide hydrolysis of rat platelets exposed to homocysteine in vitro and in vivo. In vitro homocysteine (Hcy) in the concentration range of 20 to 500 μM caused a significant decrease on ATP (around 30%) and ADP (around 45%) hydrolysis, respectively, while AMP hydrolysis was not altered. Hcy was not able to inhibit the hydrolysis of ATP and ADP catalyzed by purified apyrase at the same concentrations tested in vitro on platelets, suggesting an indirect effect. The inhibitory effect of Hcy on platelets was prevented by antioxidants agents in vitro and in vivo. Furthermore homocysteine treatment increased platelet aggregation induced by ADP. Based on the results presented herein, we propose that inhibition of extracellular ATP and ADP hydrolysis caused by homocysteine was probably due oxidative stress, since antioxidants prevented such effects. These findings may contribute to an increase platelet response to ADP and consequence development of thrombotic risk attributed to hyperhomocysteinemia.
AB - Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. Platelets play an important role in cardiovascular disease and release pro-aggregates mediators when activated, such as ADP, a physiological agonist involved in normal hemostasis and thrombosis. NTPDases and 5'-nucleotidase are ecto-enzymes that hydrolyze ATP, ADP and AMP to adenosine playing an important role on blood flow and thrombogenesis by regulating ADP catabolism. The aim of the present study was evaluate extracellular adenine nucleotide hydrolysis of rat platelets exposed to homocysteine in vitro and in vivo. In vitro homocysteine (Hcy) in the concentration range of 20 to 500 μM caused a significant decrease on ATP (around 30%) and ADP (around 45%) hydrolysis, respectively, while AMP hydrolysis was not altered. Hcy was not able to inhibit the hydrolysis of ATP and ADP catalyzed by purified apyrase at the same concentrations tested in vitro on platelets, suggesting an indirect effect. The inhibitory effect of Hcy on platelets was prevented by antioxidants agents in vitro and in vivo. Furthermore homocysteine treatment increased platelet aggregation induced by ADP. Based on the results presented herein, we propose that inhibition of extracellular ATP and ADP hydrolysis caused by homocysteine was probably due oxidative stress, since antioxidants prevented such effects. These findings may contribute to an increase platelet response to ADP and consequence development of thrombotic risk attributed to hyperhomocysteinemia.
KW - ADP
KW - ATP
KW - Homocysteine
KW - NTPDase
KW - Platelet
UR - http://www.scopus.com/inward/record.url?scp=76949099128&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76949099128&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2009.09.020
DO - 10.1016/j.thromres.2009.09.020
M3 - Article
C2 - 19850326
AN - SCOPUS:76949099128
VL - 125
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 3
ER -