A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects

M. U. Zafar, G. Vilahur, B. G. Choi, B. Ibanez, Juan Viles Gonzalez, E. Salas, Juan J. Badimon

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. Objectives: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. Patients/methods: Healthy subjects (n = 8; 32 ± 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20μM, and abciximab 4μM) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. Results: At low shear rates, LA419 displayed a reduction in thrombus area of 43% ± 8% (10μM) and 56% ± 6% (20μM), whereas at high shear rates the reductions were 44% ± 3% (10μM) and 62% ± 6% (20μM). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. Conclusions: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.

Original languageEnglish
Pages (from-to)1195-1200
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Nitric Oxide Donors
Healthy Volunteers
Blood Platelets
Fibrinogen Receptors
Thrombosis
Nitric Oxide
Nitrates
Aspirin
Coronary Artery Disease
Flow Cytometry
Cardiovascular Diseases
Perfusion
abciximab

Keywords

  • Antiplatelet agents
  • Nitric oxide
  • Thrombosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Zafar, M. U., Vilahur, G., Choi, B. G., Ibanez, B., Viles Gonzalez, J., Salas, E., & Badimon, J. J. (2007). A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects. Journal of Thrombosis and Haemostasis, 5(6), 1195-1200. https://doi.org/10.1111/j.1538-7836.2007.02543.x

A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects. / Zafar, M. U.; Vilahur, G.; Choi, B. G.; Ibanez, B.; Viles Gonzalez, Juan; Salas, E.; Badimon, Juan J.

In: Journal of Thrombosis and Haemostasis, Vol. 5, No. 6, 01.06.2007, p. 1195-1200.

Research output: Contribution to journalArticle

Zafar, MU, Vilahur, G, Choi, BG, Ibanez, B, Viles Gonzalez, J, Salas, E & Badimon, JJ 2007, 'A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects', Journal of Thrombosis and Haemostasis, vol. 5, no. 6, pp. 1195-1200. https://doi.org/10.1111/j.1538-7836.2007.02543.x
Zafar, M. U. ; Vilahur, G. ; Choi, B. G. ; Ibanez, B. ; Viles Gonzalez, Juan ; Salas, E. ; Badimon, Juan J. / A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects. In: Journal of Thrombosis and Haemostasis. 2007 ; Vol. 5, No. 6. pp. 1195-1200.
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abstract = "Background: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. Objectives: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. Patients/methods: Healthy subjects (n = 8; 32 ± 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20μM, and abciximab 4μM) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. Results: At low shear rates, LA419 displayed a reduction in thrombus area of 43{\%} ± 8{\%} (10μM) and 56{\%} ± 6{\%} (20μM), whereas at high shear rates the reductions were 44{\%} ± 3{\%} (10μM) and 62{\%} ± 6{\%} (20μM). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. Conclusions: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.",
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N2 - Background: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. Objectives: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. Patients/methods: Healthy subjects (n = 8; 32 ± 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20μM, and abciximab 4μM) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. Results: At low shear rates, LA419 displayed a reduction in thrombus area of 43% ± 8% (10μM) and 56% ± 6% (20μM), whereas at high shear rates the reductions were 44% ± 3% (10μM) and 62% ± 6% (20μM). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. Conclusions: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.

AB - Background: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. Objectives: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. Patients/methods: Healthy subjects (n = 8; 32 ± 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20μM, and abciximab 4μM) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. Results: At low shear rates, LA419 displayed a reduction in thrombus area of 43% ± 8% (10μM) and 56% ± 6% (20μM), whereas at high shear rates the reductions were 44% ± 3% (10μM) and 62% ± 6% (20μM). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. Conclusions: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.

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